Annals of Neurology最新文献

{"title":"Clonal Hematopoiesis of Indeterminate Potential Associated with Covert Cerebral Changes.","authors":"Yijuan Li, Dingding Zhang, Fei Han, Lixin Zhou, Jun Ni, Ming Yao, Zhengyu Jin, Shuyang Zhang, Liying Cui, Xinzhuang Yang, Yi-Cheng Zhu","doi":"10.1002/ana.27304","DOIUrl":"https://doi.org/10.1002/ana.27304","url":null,"abstract":"<p><strong>Objective: </strong>Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging risk factor for cardio-cerebrovascular diseases. This study aimed to investigate CHIP's association with cerebrovascular or glymphatic changes in a community-based population.</p><p><strong>Methods: </strong>This study examined Chinese community cohort participants. CHIP mutations were identified through whole-exome sequencing. Intracranial arterial stenosis, silent brain infarcts, cerebral small vessel disease markers, and diffusion along the perivascular space index were identified by magnetic resonance imaging. The correlation between CHIP and neuroimaging outcomes was investigated through univariate and multivariate logistic/linear regression. The multivariate regression model was adjusted for cerebrovascular disease risk factors, including age, sex, body mass index, smoking status, hypertension, diabetes, and hyperlipidemia.</p><p><strong>Results: </strong>In total, 18.2% (224 out of 1,229) participants were identified as carriers of CHIP mutations. The prevalence of CHIP generally increases with age (p = 0.009). After adjusting for vascular risk factors using multivariate regression, CHIP mutations were found to be significantly associated with increased odds of large magnetic resonance imaging-defined infarcts (>15 mm; OR 3.20; 95% CI 1.18 to 8.43; p = 0.018), inversely associated with diffusion along the perivascular space (β = -0.02; 95% CI -0.04 to 0; p = 0.034), and showed a borderline association with intracranial arterial stenosis (OR 1.52; 95% CI 0.99 to 2.30; p = 0.053). Notably, no statistically significant correlations were observed between CHIP and cerebral small vessel disease markers or brain atrophy measures.</p><p><strong>Interpretation: </strong>CHIP was significantly associated with glymphatic dysfunction and large infarcts, and marginally associated with intracranial arterial stenosis. Further research is needed to elucidate the pathophysiology linking CHIP to cerebral covert changes. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Electroencephalography in Predicting Post-Stroke Seizures and an Updated Prognostic Model (SeLECT-EEG).","authors":"Kai Michael Schubert, Vijaya Dasari, Ana Lúcia Oliveira, Chiara Tatillo, Gilles Naeije, Adam Strzelczyk, Giovanni Merlino, Mariarosaria Valente, Nicolas Gaspard, Vineet Punia, Marian Galovic, Carla Bentes","doi":"10.1002/ana.27301","DOIUrl":"https://doi.org/10.1002/ana.27301","url":null,"abstract":"<p><strong>Objective: </strong>Seizures negatively impact stroke outcomes, highlighting the need for reliable predictors of post-stroke epilepsy. Although acute symptomatic seizures are a known risk factor, most stroke survivors who develop epilepsy do not experience them. Early electroencephalography (EEG) findings may enhance risk prediction, particularly in patients without acute symptomatic seizures, aiding in patient management and counseling.</p><p><strong>Methods: </strong>We conducted a multicenter cohort study using data from 1,105 stroke survivors (mean age 71 years, 54% male) with neuroimaging-confirmed ischemic stroke who underwent EEG within 7 days post-stroke. Electrographic biomarkers, including epileptiform activity and regional slowing, were analyzed for their association with post-stroke epilepsy using Cox proportional hazards regression and Fine-Gray subdistribution hazard models, adjusted for differences in EEG timing and patient characteristics.</p><p><strong>Results: </strong>Post-stroke epilepsy developed in 119 patients (11%), whereas 233 (21%) had acute symptomatic seizures. The 5-year epilepsy risk was 42% (95% confidence interval [CI]: 30-49%) in patients with epileptiform activity versus 13% (95% CI: 9-16%) in those without. Regional slowing doubled the 5-year epilepsy risk (23%, 95% CI: 17-30% vs 11%, 95% CI: 7-16%). Epileptiform activity (subdistribution hazard ratio: 2.3, 95% CI: 1.5-3.4, p < 0.001) and regional slowing (subdistribution hazard ratio: 1.7, 95% CI: 1.1-2.7, p = 0.02) were independently associated with post-stroke epilepsy. A novel prognostic model, SeLECT-EEG (concordance statistic: 0.75, 95% CI: 0.71-0.80), outperformed the previous standard (SeLECT_2.0; 0.71, 95% CI: 0.65-0.76, p < 0.001).</p><p><strong>Interpretation: </strong>Electrographic biomarkers improve post-stroke epilepsy prediction beyond clinical risk factors. The SeLECT-EEG model enhances early risk stratification, particularly in patients without acute symptomatic seizures, informing management strategies and patient counseling. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the Evaluation of IVT in DOAC-Treated Stroke Patients: Addressing Methodological Considerations for Future Research","authors":"Zhengting Duan MD,&nbsp;Li Qi MD","doi":"10.1002/ana.27282","DOIUrl":"10.1002/ana.27282","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 2","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to “Enhancing the Evaluation of IVT in DOAC-Treated Stroke Patients: Addressing Methodological Considerations for Future Research”","authors":"Marius Matusevicius MD, PhD,&nbsp;Malin Säflund MD,&nbsp;Niaz Ahmed MD","doi":"10.1002/ana.27283","DOIUrl":"10.1002/ana.27283","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 2","pages":"421-423"},"PeriodicalIF":8.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"μ-Opioid Receptor Dynamics in the Parameningeal Tissue During Migraine Attacks.","authors":"Dajung J Kim, Manyoel Lim, Thiago D Nascimento, Frank Porreca, Robert A Koeppe, Nouchine Hadjikhani, Alexandre F DaSilva","doi":"10.1002/ana.27289","DOIUrl":"https://doi.org/10.1002/ana.27289","url":null,"abstract":"<p><strong>Objective: </strong>The possible impact of meningeal μ-opioid receptor (μOR) binding in migraine remains unknown. This study investigated μOR availability in the cranial parameninges involved in migraine initiation via nociceptor activation.</p><p><strong>Methods: </strong>We used positron emission tomography with [¹¹C] carfentanil, and measured μOR availability in meninges and adjacent skull bone (parameningeal tissue [PMT]) under resting and sustained thermal pain threshold stress challenge conditions. μOR availability was compared between individuals with migraine in interictal and ictal phases and healthy controls. Furthermore, we examined the relationship between μOR availability and headache intensity, as well as the potential influence of sex on this measure.</p><p><strong>Results: </strong>A total of 36 patients with interictal episodic migraine (8 also assessed ictally), 7 patients with ictal chronic migraine, and 22 healthy controls were included in the analysis. Both the episodic migraine and chronic migraine groups showed lower μOR availability in the parietal PMT than healthy controls during the ictal resting phase. No significant differences were observed during the interictal phase. Exploratory analyses on the effects of sex indicated that both healthy women and migraine patients of both sexes showed lower μOR availability in the frontal PMT compared with healthy men in the ictal sustained thermal pain threshold stress condition. Furthermore, the interictal μOR availability in the frontal PMT was negatively associated with headache intensity in the preceding month.</p><p><strong>Interpretation: </strong>The observed variability in PMT μOR availability across the different cortical regions and migraine episodes, along with its association with pain intensity, underscores the critical role of extracerebral mechanisms in migraine pathophysiology. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical Excitability as a Prognostic and Phenotypic Stratification Biomarker in Amyotrophic Lateral Sclerosis.","authors":"Federico Ranieri, Gianmaria Senerchia, Luigi Bonan, Stefania Casali, Corrado Cabona, Mariagiovanna Cantone, Fabiola De Marchi, Luca Diamanti, Alberto Doretti, Nicola Fini, Massimiliano Filosto, Andrea Fortuna, Aniello Iovino, Valentina Virginia Iuzzolino, Giuseppe Lanza, Christian Lunetta, Luca Maderna, Jessica Mandrioli, Letizia Mazzini, Gabriella Musumeci, Andi Nuredini, Gianni Sorarù, Antonella Toriello, Nicola Ticozzi, Massimiliano Todisco, Veria Vacchiano, Lucia Zinno, Vincenzo Silani, Simone Rossi, Vincenzo Di Lazzaro, Raffaele Dubbioso","doi":"10.1002/ana.27305","DOIUrl":"https://doi.org/10.1002/ana.27305","url":null,"abstract":"<p><strong>Objective: </strong>Despite its clinical heterogeneity, amyotrophic lateral sclerosis is unified by early and prominent alterations in cortical excitability, increasingly recognized as contributors to disease progression. This study assessed whether the ratio between motor evoked potential (MEP) amplitude, reflecting upper motor neuron integrity, and compound muscle action potential (CMAP) amplitude, indexing lower motor neuron function, could provide an accessible marker of corticospinal excitability to stratify patients by phenotype, stage, and survival.</p><p><strong>Methods: </strong>In this multicenter retrospective study, 743 amyotrophic lateral sclerosis patients from 16 tertiary centers in Italy were analyzed. The MEP:CMAP ratio, recorded from upper limb muscles, was categorized as hyperexcitable, normal, or hypoexcitable. Phenotypes included progressive muscular atrophy (or lower motor neuron), flail arm/leg, classic, bulbar, patient with predominant upper motor neuron signs (or pyramidal), and primary lateral sclerosis. Disease stage was assessed using King's staging. Survival was analyzed using Kaplan-Meier curves and Cox regression models.</p><p><strong>Results: </strong>The MEP:CMAP ratio differed significantly across phenotypes (p < 0.0001), with hyperexcitability predominating in lower motor neuron, flail, classic, and bulbar forms, and hypoexcitability in pyramidal and primary lateral sclerosis. Hypoexcitability increased in advanced King's stages (p < 0.0001). Hyperexcitable patients had shorter survival (p = 0.004), including when tested within 1 year of onset (p = 0.006). Cox regression identified the MEP:CMAP ratio as an independent survival predictor (HR 1.84, 95% CI 1.12-3.03, p = 0.016).</p><p><strong>Interpretation: </strong>This real-world study supports the clinical value of the MEP:CMAP ratio as a scalable biomarker of cortical excitability in amyotrophic lateral sclerosis, with prognostic relevance across phenotypes and disease stages. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Dose Pulse Glucocorticoid Treatment Prevents White Matter Spinal Cord Pseudoatrophy in Newly Diagnosed Multiple Sclerosis.","authors":"Simone Sacco, Nico Papinutto, Vinicius A Schoeps, Shuiting Cheng, William A Stern, Haojun Zhao, Antje Bischof, Eduardo Caverzasi, Manula Dombagahawatta, Jeremy Juwono, Amit Akula, Christian Cordano, Alexandra Beaudry-Richard, Refujia Gomez, Meagan Harms, Adam Santaniello, Riley M Bove, Jeffrey M Gelfand, Douglas S Goodin, Ari J Green, Jorge R Oksenberg, Emmanuelle Waubant, Michael R Wilson, Scott S Zamvil, Bruce A C Cree, Stephen L Hauser, Roland G Henry","doi":"10.1002/ana.27298","DOIUrl":"https://doi.org/10.1002/ana.27298","url":null,"abstract":"<p><strong>Objective: </strong>Spinal cord (SC) atrophy correlates with and predicts the underlying progressive biology in active and non-active multiple sclerosis (MS), thereby providing a biomarker for clinical trials and patient management. Initiation of disease-modifying therapy (DMT) may be followed by early pronounced central nervous system (CNS) volume loss due to resolution of inflammation (pseudoatrophy) and confounding the interpretation of atrophy. High-dose glucocorticoids (HDGs) reduce inflammation and might therefore modify pseudoatrophy.</p><p><strong>Methods: </strong>One hundred twenty-three newly diagnosed and DMT-naïve MS participants (relapsing-remitting, 70% female participants, median age = 36 years, Expanded Disability Status Scale [EDSS] 2.0) were followed for up to 3 years. Forty-two participants received HDG before baseline magnetic resonance imaging (MRI; DMT-HDG; median = 52 days, interquartile range [IQR] = 37-71), whereas 60 did not (DMT/no-HDG). Twenty-one participants remained untreated (no-DMT), and 102 started DMT after baseline MRI. SC total cervical cord cross-sectional area (TCA), gray matter area (GMA), and white matter area (WMA) and regional brain volumes were analyzed using mixed effects models.</p><p><strong>Results: </strong>The DMT-HDG, DMT/no-HDG, and no-DMT groups had similar demographic, clinical, and radiological features. Pronounced SC pseudoatrophy was observed based on more year 1 versus year 2 volume loss for DMT/no-HDG (-2.06% vs. 0.83%; P = 0.02) but not DMT-HDG (-0.51% vs. 0.66%; P = 0.8) and more year 1 volume loss for DMT/no-HDG compared to DMT-HDG (-2.06% vs. 0.51%; P = 0.02).</p><p><strong>Interpretation: </strong>HDG preceding baseline MRI suppresses CNS white matter (WM) pseudoatrophy after DMT initiation, most conspicuously for the SC. Suppression of pseudoatrophy with HDG may improve the fidelity of clinical trials and enhance the feasibility for short-term trials with SC and brain MRI outcomes in active MS by pretreatment with HDG. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Genetic Findings in a Chinese Cohort of Dentatorubral-Pallidoluysian Atrophy Patients.","authors":"Ru-Ying Yuan, Ya-Fang Chen, Wei Lin, Meng-Cheng Li, Yi-Heng Zeng, Bi Cheng, Xin-Tong Yu, Dan-Dan Zuo, Hua-Mei Sun, Bei-Ning Ye, Ying-Xin Ye, Mao-Lin Cui, Nai-Qing Cai, Yu Lin, Qi-Jie Zhang, Yu-Sen Qiu, Lin-Wei Zhang, Xing-Wang Song, Jia-Na Wei, Li-Ying Pan, Ya-Yun Yan, Yi-Min Sun, Jin-Tai Yu, Zhi-Ying Wu, Yi Dong, Chun-Yan Cao, Chao Wu, Jie Zu, Yuan-Yuan Dai, Xian-Jin Shang, Hai-Tao Zhou, Min-Jin Wang, Qing Ke, En-Lin Dong, Yi-Feng Xiao, Zi-Yue Ouyang, Xin-Yuan Chen, Jian-Ping Hu, Min-Ting Lin, Ying Fu, Wan-Jin Chen, Ning Wang, Shi-Rui Gan","doi":"10.1002/ana.27293","DOIUrl":"https://doi.org/10.1002/ana.27293","url":null,"abstract":"<p><strong>Objective: </strong>Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, inherited neurodegenerative disorder caused by the expansion of cytosine-adenine-guanine repeats in ATN1. Most studies on DRPLA to date are limited to case reports. We aimed to provide a comprehensive summary of the clinical, genetic, biological, and magnetic resonance imaging characteristics of DRPLA using cross-sectional baseline data.</p><p><strong>Methods: </strong>This is a cross-sectional observational cohort study. We used an extensive battery of assessments, included clinical phenotypes, genotypes, cognitive performance, biological markers, and magnetic resonance imaging characteristics.</p><p><strong>Results: </strong>We enrolled 116 DRPLA patients, including 96 manifest patients and 20 prodromal patients. We identified a previously unreported ATN1 haplotype consisting of 8 single-nucleotide polymorphisms. Cognitive assessments revealed that 51 manifest patients (96%) and 4 prodromal patients (29%) scored <26 on the Montreal Cognitive Assessment. Manifest patients showed impairments across all cognitive domains, whereas prodromal patients showed deficits only in phonemic fluency. Biological analyses showed significantly elevated plasma neurofilament light levels in manifest patients compared with prodromal patients (P < 0.001) and healthy controls (P < 0.001). Magnetic resonance imaging findings revealed widespread gray matter loss across the whole brain in manifest patients, whereas prodromal patients showed gray matter loss localized to the bilateral cerebellar hemispheres.</p><p><strong>Interpretation: </strong>This is the first DRPLA cohort study to comprehensively report clinical, genetic, cognitive, imaging, and plasma neurofilament light data. This study provides robust data to enhance our understanding of the overall features of DRPLA. We also propose clear definitions for the preclinical stage of DRPLA, and demonstrate the high diagnostic utility of plasma neurofilament light as a biomarker. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease Characteristics and Treatments Associated with Outcome in Primary Angiitis of the Central Nervous System-A Multicenter Cohort Study in 163 Patients.","authors":"Anna Lena Fisse, Nadine Bonberg, Carolin Beuker, Claudia Pfeuffer, Andreas Heidenreich, Christina Krüger, Milani Deb-Chatterji, Jana Becker, Stefan T Gerner, Clemens Küpper, Louisa Nitsch, Roxane-Isabelle Kestner, Lars Udo Krause, Juliane Herm, Alexander Katalinic, André Karch, Ralf Gold, Heinz Wiendl, Wolf-Rüdiger Schäbitz, Gabor C Petzold, Waltraud Pfeilschifter, Marius Ringelstein, Thorsten R Doeppner, Lars Kellert, Hagen B Huttner, Markus Kraemer, Tim Magnus, Karl Georg Haeusler, Heike Minnerup, Jens Minnerup","doi":"10.1002/ana.27295","DOIUrl":"https://doi.org/10.1002/ana.27295","url":null,"abstract":"<p><strong>Objective: </strong>The aim was to determine patient, disease, and treatment characteristics associated with outcome in patients with primary angiitis of the central nervous system (PACNS) in a large multicenter German cohort.</p><p><strong>Methods: </strong>In a retrospective, observational cohort study, we analyzed 163 adult patients who met the diagnostic criteria for PACNS. Data were collected from January 2004 to December 2018 in 13 tertiary care centers in Germany. Survival, recurrence-free survival and long-term global disability were assessed.</p><p><strong>Results: </strong>Of 163 patients with PACNS (median [interquartile range (IQR)] age 48 [39-59.5] years; 73 [45%] women), 29 (18%) died, 84 (52%) had a poor outcome (modified Rankin scale [mRS] 3-6 at last follow-up), and 82 (50%) patients relapsed. Poorer survival was associated with patient age (hazard ratio [HR], 1.96 [95% confidence interval (CI), 1.41-2.74] per 10 years), longer time between initial manifestation and diagnosis (HR, 1.01 [95% CI, 1.00-1.01] per month), and necrotizing subtype (HR, 10.2 [95% CI, 2.18-48.2]). Long-term disability was associated with older age (odds ratio [OR], 1.40 [95% CI, 1.07-1.86] per 10 years), and worse mRS score at diagnosis (OR, 4.43 [95% CI, 1.97-10.4]). Patients treated with cyclophosphamide alone or in combination with steroids had a lower incidence of relapse than untreated patients (HR, 0.44 [95% CI, 0.22-0.86]; HR, 0.47 [95% CI, 0.24-0.92]).</p><p><strong>Interpretation: </strong>In patients with PACNS, the long-term outcome depends on several patient and disease characteristics. Our results favor treatment with cyclophosphamide alone or in combination with steroids, because this was associated with a reduction in the relapse rate. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The FindMNDBiomarker Program: Protein Changes in Motor Neuron Disease/Amyotrophic Lateral Sclerosis Postmortem Tissue and Biofluids.","authors":"Gabrielle L Adler, Matthew C Kiernan, Rachel H Tan","doi":"10.1002/ana.27300","DOIUrl":"10.1002/ana.27300","url":null,"abstract":"<p><strong>Objective: </strong>Biomarkers of disease pathogenesis are critically needed for amyotrophic lateral sclerosis (ALS) to facilitate diagnosis and patient stratification into appropriate therapeutic trials. Proteomic studies offer significant potential to advance this, but reproducibility across laboratories is a key component toward identifying protein changes that can be translated into clinical applications.</p><p><strong>Methods: </strong>A combined analysis of 25 proteomic studies in human ALS biospecimens was performed to identify proteins consistently altered in ALS postmortem tissue, cerebrospinal fluid, or blood, as well as across primary regions of ALS pathology and peripheral biofluids. We consolidated these datasets into a user-friendly database \"FindMND Biomarker,\" which is an accessible search tool that allows users to quickly determine how often, and in which biospecimen types, their proteins of interest are dysregulated in patients with ALS.</p><p><strong>Results: </strong>Our combined analysis identified 1,458 altered proteins in ALS, and revealed consistent dysregulation in mitochondrial, cytoplasmic, and RNA binding proteins in primary and later affected regions of ALS pathology. Remarkable consistency in the direction and dysregulation of chitinases and gelsolin proteins were observed across ALS biofluids. Comparisons of postmortem tissue and biofluids reinforce several known protein changes, and highlighted novel proteins of interest that may drive disease pathogenesis.</p><p><strong>Interpretation: </strong>The biospecimen type in which protein dysregulation is most consistently identified provides important insight into disease, and whether these represent potential measures of disease pathogenesis or systemic changes. By streamlining proteins by reproducibility and biospecimen type, FindMNDBiomarker is a useful resource that provides new mechanistic insights, and facilitates the prioritization of ALS-associated proteins for further validation and investigation. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}