Annals of Clinical and Translational Neurology最新文献

{"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}

{"title":"Longitudinal Assessment of Biomarkers in ALS: Discriminative Biomarkers for Disease Progression and Survival","authors":"David R. Beers,&nbsp;Yueh-Yun Lin,&nbsp;Jason R. Thonhoff,&nbsp;Aaron D. Thome,&nbsp;Alireza Faridar,&nbsp;Weihua Zhao,&nbsp;Shixiang Wen,&nbsp;Stanley H. Appel","doi":"10.1002/acn3.70381","DOIUrl":"10.1002/acn3.70381","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess the association and discriminative performance of serum biomarkers with clinical disease progression and survival in patients with amyotrophic lateral sclerosis (ALS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study, conducted at Houston Methodist Hospital, Houston, TX, used longitudinal serum samples collected between January 2018 and December 2022. A cohort of 100 patients with sporadic or familial ALS was randomly selected and assayed by ELISAs for biomarkers 4-hydroxy-2-nonenal (4-HNE), lipopolysaccharide binding protein (LBP), and neurofilament light chain (NfL) levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Each biomarker was increased in patients. 4-HNE and LBP were increased at diagnosis and continued to increase as the disease progressed; both correlated with progression rates and survival. NfL was increased at diagnosis, then plateaued relatively. LBP correlated with ALSFRS-R at diagnosis; NfL did not correlate. 4-HNE and LBP were increased in bulbar onset patients who survived a shorter period of time; NfL levels for bulbar/limb onsets were not different. Receiver operating characteristic analyses with apparent and optimism-adjusted area-under-the-curve (AUC) demonstrated that 4-HNE and LBP discriminated rapid progression and survival, whereas NfL showed modest discrimination for rapid progression. The combination of biomarkers yielded improved AUCs as depicted in Venn diagrams across individual and combined biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>4-HNE, LBP, and NfL are biomarkers of lipid peroxidation, systemic inflammation, and axonal integrity. 4-HNE and LBP correlated with disease burden, disease progression, and survival. In the bulbar onset, survival was shortened and associated with increased 4-HNE and LBP. This exploratory longitudinal study suggests the utility of combining biomarkers to discriminate disease progression and survival and monitor clinical trial outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2102-2113"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626444","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":"GAD65 Antibody ELISA With Extended Reportable Range: Validation and Guidance for Neurological Practice","authors":"Andrew McKeon,&nbsp;Dana Olofson,&nbsp;Diana Anissian,&nbsp;Divyanshu Dubey,&nbsp;Eoin P. Flanagan,&nbsp;Max C. Herman,&nbsp;Sarosh R. Irani,&nbsp;Daniel H. Lachance,&nbsp;Maria A. Willrich,&nbsp;Sean Pittock,&nbsp;John R. Mills,&nbsp;Anastasia Zekeridou","doi":"10.1002/acn3.70378","DOIUrl":"10.1002/acn3.70378","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To (1) validate GAD65-ELISA detection and quantification for type 1 diabetes mellitus and autoimmune neurological diagnoses, (2) correlate ELISA results (reference range &lt; 5 IU/mL) with established radioimmunoprecipitation assay (RIA; ≤ 0.02 nmol/L), and (3) define ELISA clinical utility and pitfalls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Serum performance for diabetes (FDA-cleared, undiluted) was verified, and neurological laboratory-developed serum and CSF dilution protocols were validated to extend the reportable range beyond &gt; 250 IU/mL. ELISA and RIA values were correlated, including established neurological RIA cut-offs (serum ≥ 20 nmol/L; CSF any positive).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ELISA met analytical criteria (precision, accuracy, sensitivity, specificity, reference range) in serum and CSF and was clinically equivalent to RIA for autoimmune diabetes. Neurological ELISA cut-offs were established at 10,000 IU/mL (serum) and 100 IU/mL (CSF). Precision was better below 10,000 IU/mL (CVs &lt; 20%) than above (CVs 30.8% serum; 26.5% CSF). ELISA–RIA correlation and agreement was stronger below the neurological cut-off (R² = 0.89) than above (R² = 0.36). Positive agreement for RIA-defined neurological disease was 100% in serum and CSF; all serums were &gt; 10,000 IU/mL. Clinical specificity was 97.5% in serum and 100% in CSF, exceeding reported RIA specificity. Screen results &gt; 250 IU/mL spanned a wide range of dilution values; many were below the neurological cut-off. Most patients with paired serum/CSF positivity showed elevated GAD65 IgG indices.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>GAD65 ELISA and RIA have equivalent sensitivity for autoimmune diabetes and neurological testing, with higher specificity for ELISA. A serum cut-off of 10,000 IU/mL is informative but requires clinical context, and dilution of screen &gt; 250 IU/mL samples is essential for neurological interpretation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2036-2045"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571273","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":"Relationship Between Neurologic Symptoms and Signs and FMR1 Genotype in Premutation Carriers","authors":"Flora Tassone,&nbsp;Freddy Chafota,&nbsp;Miguel E. Rentería,&nbsp;Randi J. Hagerman,&nbsp;Ellery Santos,&nbsp;Anna Atkinson,&nbsp;Nicholas G. Martin,&nbsp;Elsdon Storey,&nbsp;Danuta Z. Loesch","doi":"10.1002/acn3.70375","DOIUrl":"10.1002/acn3.70375","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is the most severe late-onset condition caused by a premutation in the <i>FMR1</i> gene, characterized by expanded CGG triplet repeats of 55–200. Clinical presentations of FXTAS, including gait ataxia, kinetic tremor, cognitive decline, and rare Parkinsonism, are linked to white matter degeneration, predominantly in the middle cerebellar peduncles. Underlying pathophysiological mechanisms involve the sequestration of CGG-binding proteins due to elevated <i>FMR1</i> mRNA and repeat-associated non-AUG (RAN)-initiated translation. Outside of the full presentation of FXTAS, some FMR1 premutation carriers exhibit only isolated clinical changes occurring in this syndrome. This study explored the relationship of molecular predictors of disease, either with these isolated features in patients who did not meet diagnostic criteria for FXTAS or with diagnosable FXTAS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>176 male (<i>N</i> = 111) and female (<i>N</i> = 65) premutation carriers were separated into three groups based on neurological/cognitive examination data: asymptomatic, non-syndromic/presenting isolated changes, and syndromic-FXTAS. These categories were then separately correlated with CGG repeat length and FMR1 mRNA expression levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Regression and distributions' analyses showed that the most consistent associations of both genomic markers were with neurological severity rankings, followed by a binary definition of FXTAS status. Among other minor presentations, Parkinsonism and cognitive impairment were significantly correlated with CGG size in male samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>This data provides evidence for a linear relationship between <i>FMR1</i> CGG size and mRNA levels, as well as both syndromic and non-syndromic forms of neurological manifestations, which represent aspects of the premutation-linked neurodegenerative process that persist with advancing age.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2068-2077"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147588891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes of SEEG-Guided Radiofrequency Thermocoagulation in Children With Focal Drug-Resistant Epilepsy: A Multicenter Real-World Study","authors":"Weitao Chen,&nbsp;Stéphane Jean,&nbsp;Weihong Liu,&nbsp;Yihai Dai,&nbsp;Xinrong Fang,&nbsp;Xiaoqiang Wei,&nbsp;Shan Chen,&nbsp;Shiwei Song","doi":"10.1002/acn3.70373","DOIUrl":"10.1002/acn3.70373","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) has emerged as a safe and effective minimally invasive treatment for children with drug-resistant focal epilepsy. Although evidence from real-world studies remains limited, numerous pediatric cases have demonstrated promising outcomes. This retrospective study aimed to evaluate the seizure outcomes of SEEG-RFTC in pediatric patients and identify predictive factors associated with seizure freedom.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective observational study was conducted across two epilepsy centers, including 111 children with drug-resistant epilepsy who underwent SEEG-RFTC. Postoperative outcomes were assessed primarily by the rate of seizure freedom at the last follow-up (minimum 1 year). Potential predictive factors were analyzed through comparisons of clinical, neuroimaging, electrophysiological, and etiological variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All patients were followed for at least 1 year post-procedure, with 73 (65.8%) achieving seizure freedom. Among 46 patients with focal cortical dysplasia, the seizure-free rate was 80.4%. In 10 patients with hippocampus sclerosis, 6 (60%) were seizure-free at the final follow-up. Statistical analysis identified the course of illness (<i>p</i> &lt; 0.01) and positron emission tomography (PET) findings (<i>p</i> = 0.01) as significant predictors of seizure freedom.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SEEG-RFTC is a safe procedure that yields favorable outcomes in a substantial proportion of pediatric patients with drug-resistant focal epilepsy. The duration of epilepsy and PET characteristics are significantly associated with the likelihood of achieving seizure freedom. These findings highlight the potential of SEEG-RFTC as a valuable therapeutic option in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2027-2035"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519470","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":"Human Pegivirus Encephalitis With Brain Detection and Response to Sofosbuvir Ledipasvir","authors":"Antoine Moulignier,&nbsp;Françoise Heran,&nbsp;Francis Lallemand,&nbsp;Pierre Bourdillon","doi":"10.1002/acn3.70450","DOIUrl":"10.1002/acn3.70450","url":null,"abstract":"<p>Human pegivirus (HPgV-1) has been associated with severe encephalomyelitis in immunocompromised patients. Its neurological spectrum remains poorly defined. We report a slowly progressive encephalitis in a person living with well-controlled HIV, characterized by white matter abnormalities and inflammatory cerebrospinal fluid (CSF). HPgV RNA was detected in CSF and brain tissue by metagenomic sequencing, with no alternative pathogen identified. Following off-label treatment with sofosbuvir/ledipasvir, the patient showed sustained clinical improvement, normalization of CSF findings, and disappearance of detectable HPgV RNA. This observation expands the clinical context of HPgV-1 detection and supports further investigation of its role in central nervous system disease.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2138-2142"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196747","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":"Added Prognostic Value of EEG Reactivity in Comatose Patients Following Cardiac Arrest","authors":"Sarah Caroyer,&nbsp;Marie Obrecht,&nbsp;Charlotte de Maeseneire,&nbsp;Charlotte Damien,&nbsp;Chantal Depondt,&nbsp;Lorenzo Ferlini,&nbsp;Estelle Rikir,&nbsp;Filippo Annoni,&nbsp;Fabio Silvio Taccone,&nbsp;Nicolas Mavroudakis,&nbsp;Benjamin Legros,&nbsp;Nicolas Gaspard","doi":"10.1002/acn3.70388","DOIUrl":"10.1002/acn3.70388","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To evaluate the added prognostic value of EEG reactivity for favorable outcome compared with background analysis during and after targeted temperature management (TTM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Prospective observational cohort study of comatose post–cardiac arrest patients admitted to a single academic center between 2017 and 2022, all undergoing continuous EEG monitoring. Reactivity was assessed using standardized definitions and stimulation protocols. EEG background was classified by continuity and amplitude according to consensus criteria. Favorable outcome was defined as CPC 1–2 at discharge or 3 months. Prognostic performance of background and reactivity, alone or combined in a multimodal process, was evaluated with sensitivity, specificity, likelihood ratios, accuracy, and balanced accuracy. A literature review was performed on the prognostic value of reactivity testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>313 patients underwent reactivity testing during and 252 after TTM. Background assessment demonstrated very high sensitivity (98%–100%) but modest specificity (34%–58%). Reactivity alone had lower sensitivity (82%–93%) with slightly higher specificity. Combining background and reactivity increased specificity (53%–58% to 71%) and overall accuracy. In patients with non–highly malignant backgrounds, reactivity improved sensitivity (60% to 84%–90%) but reduced specificity (74% to 51%–55%). Patterns were consistent for survival and in the context of multimodal prognostication. Literature review showed similar findings despite heterogeneity in definitions and methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>EEG reactivity should not guide WLST decisions alone, but its presence reliably indicates a higher likelihood of a favorable outcome. Optimized interpretation modestly improves prognostic accuracy but does not substantially enhance multimodal prediction, highlighting the need for further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2088-2101"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621326","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 Role of Calcitonin Gene-Related Peptide in High-Altitude Headache: A Prospective Field Study","authors":"Roman Schniepp,&nbsp;Ludwig Karrasch,&nbsp;Helena Breitenstein,&nbsp;Andreas Straube,&nbsp;Katharina Kamm","doi":"10.1002/acn3.70374","DOIUrl":"10.1002/acn3.70374","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>High-altitude headache (HAH) is a common neurological condition associated with rapid ascent to high altitude. The pathophysiological mechanisms underlying HAH remain incompletely understood. Calcitonin gene-related peptide (CGRP), a neuropeptide implicated in migraine pathophysiology, may play a key role in the pathophysiology of the disorder due to the shared clinical presentation of migraine and HAH. This study investigated tear fluid CGRP concentrations in response to high-altitude exposure and headache in healthy volunteers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective field study was conducted during a high-altitude trekking expedition in the Alps. Headache and accompanying symptoms were raised using a structured questionnaire, and tear fluid samples were collected at study Day 1 (baseline, 450 m), at study Day 3 (3647 m), and at study Day 4 (4554 m). Tear fluid CGRP concentrations were quantified using a commercial ELISA kit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirteen participants were included in the analysis. At 4554 m, 61.5% of participants reported a HAH. In participants with HAH, increase of tear fluid CGRP was significantly higher compared to participants without HAH (HAH: +1.49 ± 1.74 ng/mL, no HAH: −0.42 ± 0.64 ng/mL; <i>p</i> = 0.011). Increase of tear fluid CGRP levels was significantly higher in participants with a moderate-to-severe headache (+1.86 ± 1.86 ng/mL) compared to participants with mild headache (−0.19 ± 0.75 ng/mL; <i>p</i> = 0.008).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The results support a potential role for CGRP in the pathophysiology of HAH. Further studies with a larger number of participants are needed to determine the mechanisms of the disorder.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2046-2056"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571299","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":"High-Resolution MRI Revealed Different Etiology-Specific Associations With Cerebral Infarction in Adult Moyamoya Vasculopathy","authors":"Guangsong Han,&nbsp;Jiachun Pan,&nbsp;Yuehui Hong,&nbsp;Xiaoyuan Fan,&nbsp;Ming Yao,&nbsp;Lixin Zhou,&nbsp;Yicheng Zhu,&nbsp;Feng Feng,&nbsp;Jun Ni","doi":"10.1002/acn3.70380","DOIUrl":"10.1002/acn3.70380","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>High-resolution MRI enables detailed assessment of intracranial vessel wall pathology in moyamoya vasculopathy. We aimed to classify adult moyamoya vasculopathy etiologies using high-resolution MRI and to examine subtype-specific associations between high-resolution MRI features and ischemic infarction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 398 adult patients with moyamoya vasculopathy. According to high-resolution MRI characteristics, 340 patients were classified as moyamoya disease (<i>n</i> = 279) or atherosclerosis-associated moyamoya vasculopathy (<i>n</i> = 61). Hemisphere-level analyses were performed using generalized estimating equations logistic models with patients as clusters to evaluate associations between high-resolution MRI measures and ischemic hemispheres.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with atherosclerosis-associated moyamoya vasculopathy, moyamoya disease patients were more often female and more likely to have a family history of early-onset stroke and posterior cerebral artery involvement. In the moyamoya disease group, greater middle cerebral artery stenosis, higher Suzuki stage, and more severe internal carotid artery, middle cerebral artery, and posterior cerebral artery involvement were independently associated with ischemic hemispheres, whereas a higher middle cerebral artery remodeling index was inversely associated with ischemia. In the atherosclerosis-associated moyamoya vasculopathy group, higher middle cerebral artery remodeling index and more severe anterior cerebral artery involvement were independently associated with ischemic hemispheres, while other high-resolution MRI metrics showed no significant associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>High-resolution MRI-derived quantitative vascular metrics show distinct ischemia-related patterns in moyamoya disease and atherosclerosis-associated moyamoya vasculopathy. Global steno-occlusive burden with impaired middle cerebral artery remodeling characterizes ischemic hemispheres in moyamoya disease, whereas adverse middle cerebral artery remodeling and anterior cerebral artery involvement are key correlates of ischemia in atherosclerosis-associated moyamoya vasculopathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 10","pages":"2057-2067"},"PeriodicalIF":3.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147588877","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}