Annals of Neurology最新文献

{"title":"Cost-Effectiveness of Endovascular Thrombectomy in Patients with Large Ischemic Stroke.","authors":"Lan Gao, Leonid Churilov, Hannah Johns, Deep Pujara, Ameer E Hassan, Michael Abraham, Santiago Ortega-Gutierrez, Muhammad Shazam Hussain, Michael Chen, Spiros Blackburn, Clark W Sitton, Florentina M E Pinckaers, Wim H van Zwam, Georgios Tsivgoulis, Michael D Hill, James C Grotta, Scott Kasner, Marc Ribo, Bruce C Campbell, Amrou Sarraj","doi":"10.1002/ana.27119","DOIUrl":"10.1002/ana.27119","url":null,"abstract":"<p><strong>Objectives: </strong>Whereas highly cost-effective and cost-saving for patients with small infarcts, whether endovascular thrombectomy (EVT) remains cost-effective in patients with extensive ischemic injury is uncertain.</p><p><strong>Methods: </strong>We conducted a model-based cost-effectiveness analysis from the United States, Australian, and Spanish societal perspectives, using a 7-state Markov model, with each state defined by the modified Rankin Scale (mRS) score. Initial probabilities at 3 months were derived from the SELECT2 trial. All other model inputs, including transition probabilities, health care and non-health care costs, and utility weights, were sourced from published literature and government websites. Our analysis included extensive sensitivity and subgroup analyses.</p><p><strong>Results: </strong>EVT in patients with large ischemic stroke improved health outcomes and was associated with lower costs from a societal viewpoint. EVT was cost-effective with a mean between-group difference of 1.24 quality-adjusted life years (QALYs), and a cost-saving of $23,409 in the United States, $10,691 in Australia, and $30,036 in Spain, in addition to uncosted benefits in productivity for patients and carers. Subgroup analyses were directionally consistent with the overall population, notably with preserved cost-effectiveness in older patients (≥ 70 years) and those with more severe strokes (National Institutes of Health Stroke Scale [NIHSS] ≥ 20). Sensitivity analyses were largely consistent with the base-case results.</p><p><strong>Interpretation: </strong>EVT demonstrated cost-effectiveness in patients with large core across different settings in the United States, Australia, and Spain, including older patients and those with more severe strokes. These results further support adaptation of systems of care to accommodate the expansion of thrombectomy eligibility to patients with large cores and maximize EVT benefits. ANN NEUROL 2025;97:222-231.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"222-231"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542308","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":"Balamuthia Mandrillaris Encephalitis Post-Raw Beef Ingestion.","authors":"Yongqin Xiong, Xin Lou","doi":"10.1002/ana.27082","DOIUrl":"10.1002/ana.27082","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"384-385"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337701","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":"Fighting Amyotrophic Lateral Sclerosis by Protecting the Liver? A Prospective Cohort Study.","authors":"Luyi Zhu, Yaojia Li, Xinyue Yu, Yinuo Chen, Junwei Zhang, Chunyang Pang, Jiali Xie, Lingfei Gao, Lihuai Du, Wen Cao, Dongsheng Fan, Can Cui, Huan Yu, Binbin Deng","doi":"10.1002/ana.27115","DOIUrl":"10.1002/ana.27115","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have observed liver abnormalities in amyotrophic lateral sclerosis (ALS) patients. This study aimed to investigate whether early signs of liver disease, measured by magnetic resonance imaging-derived iron-corrected T1-mapping (cT1), are risk factors for developing ALS.</p><p><strong>Methods: </strong>cT1 and proton density fat fraction were measured and automatically analyzed using LiverMultiScan® software. The Fibrosis-4 index was calculated using an established formula based on age and blood markers. Cox proportional hazard models were used to examine the relationship between liver disease, liver biomarkers, and incident ALS.</p><p><strong>Results: </strong>In a cohort of 533,707 individuals from UK Biobank, 24 ALS cases were identified among 28,328 participants with liver disease during the follow-up period. Among a total of 33,959 individuals with complete liver imaging data, 15 incident ALS cases were observed during a median follow-up period of 5.6 years. Individuals with liver disease had a higher risk of developing ALS, with an adjusted hazard ratio of 7.35 (95% CI 4.47-12.09; p < 0.001). An increase in cT1 was also associated with a higher risk of ALS. After adjusting for age, sex, Townsend deprivation index, smoking status, alcohol intake frequency, body mass index, proton density fat fraction, Fibrosis-4, and metabolic syndrome, an increase in cT1 remained significantly associated with a higher risk of ALS, with an adjusted hazard ratio of 3.15 (95% CI 1.79-5.55) per 1-SD increase. Sensitivity analyses confirmed these robust results.</p><p><strong>Interpretation: </strong>Liver disease activity, indicated by cT1, increases the risk of developing ALS, independent of metabolic syndrome, liver fat, or fibrosis. ANN NEUROL 2025;97:270-280.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"270-280"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453961","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":"Recessive Variants in PIGG Cause a Motor Neuropathy with Variable Conduction Block, Childhood Tremor, and Febrile Seizures: Expanding the Phenotype.","authors":"Christopher J Record, Antoinette O'Connor, Nienke E Verbeek, Wouter van Rheenen, Eleni Zamba Papanicolaou, Stojan Peric, Peter C Ligthart, Mariola Skorupinska, Ellen van Binsbergen, Philippe M Campeau, Vukan Ivanovic, Brian Hennigan, John C McHugh, Julian C Blake, Yoshiko Murakami, Matilde Laura, Sinéad M Murphy, Mary M Reilly","doi":"10.1002/ana.27113","DOIUrl":"10.1002/ana.27113","url":null,"abstract":"<p><p>Biallelic variants in phosphatidylinositol glycan anchor biosynthesis, class G (PIGG) cause hypotonia, intellectual disability, seizures, and cerebellar features. We present 8 patients from 6 families with a childhood-onset motor neuropathy and neurophysiology demonstrating variable motor conduction block and temporal dispersion. All individuals had a childhood onset tremor, 5 of 8 had cerebellar involvement, and 6 of 8 had childhood febrile seizures. All individuals have biallelic PIGG variants, including the previously reported pathogenic variant Trp505*, plus 6 novel variants. Null enzyme activity is demonstrated via PIGO/PIGG double knockout system for Val339Gly and Gly19Glu, and residual activity for Trp505* due to read-through. Emm negative blood group status was confirmed in 1 family. PIGG should be considered in unsolved motor neuropathy. ANN NEUROL 2025;97:388-396.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"388-396"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NORSE, FIRES, and a Polygenic Trickle of Autoimmunity.","authors":"Ingo Helbig, Shiva Ganesan","doi":"10.1002/ana.27148","DOIUrl":"10.1002/ana.27148","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"386-387"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Early-Life and Premorbid Measurements of Body Composition and Risk of Motor Neuron Disease: A Prospective Cohort Study in the UK Biobank.","authors":"Emily E Joyce, Shishi Xu, Caroline Ingre, Rosa Luisa Potenza, Christina Seitz, Huazhen Yang, Yu Zeng, Huan Song, Fang Fang","doi":"10.1002/ana.27109","DOIUrl":"10.1002/ana.27109","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to investigate the association between developmental and premorbid body composition measurements and the risk of motor neuron disease (MND).</p><p><strong>Methods: </strong>We performed a cohort study in the UK Biobank to assess the association of developmental body metrics and premorbid body composition measures (using 28 measurements and 7 patterns of body composition) with the risk of MND. Among participants with longitudinal measures, we compared the changes in body composition over time between individuals who later developed MND and those who remained free of MND.</p><p><strong>Results: </strong>Among the 412,691 individuals included in this study, 549 people received an MND diagnosis during the follow-up visit. Higher birth weight was associated with an increased risk of MND among individuals born over 4 kg (hazard ratio [HR] per kg increase = 2.21, 95% confidence interval [CI] = 1.38-3.55), and taller adult height was associated with an increased risk of MND (HR per 5 cm increase = 1.10, 95% CI = 1.03-1.17). We observed that measures of elevated fat mass were associated with a lower risk of MND more than 5 years before diagnosis. A higher \"leg-dominant fat distribution\" pattern was associated with an increased risk whereas higher \"muscle strength\" was associated with a reduced risk of MND 5 years before diagnosis. Longitudinal analyses indicated a faster decline in measures of fat mass and muscle strength, as well as a shift in fat distribution from arm to leg dominant, among individuals who later developed MND, compared with others.</p><p><strong>Interpretation: </strong>Body composition at early and middle age may be indicative of the risk of MND development. ANN NEUROL 2025;97:259-269.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"259-269"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurologic Manifestations of Long COVID Disproportionately Affect Young and Middle-Age Adults.","authors":"Natasha A Choudhury, Shreya Mukherjee, Tracey Singer, Aditi Venkatesh, Gina S Perez Giraldo, Millenia Jimenez, Janet Miller, Melissa Lopez, Barbara A Hanson, Aasheeta P Bawa, Ayush Batra, Eric M Liotta, Igor J Koralnik","doi":"10.1002/ana.27128","DOIUrl":"10.1002/ana.27128","url":null,"abstract":"<p><strong>Objective: </strong>To investigate neurologic manifestations of post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients across the adult lifespan.</p><p><strong>Methods: </strong>Cross-sectional study of the first consecutive 200 PNP and 1,100 NNP patients evaluated at a Neuro-coronavirus disease 2019 (COVID-19) clinic between May 2020 and March 2023. Patients were divided into younger (18-44 years), middle-age (45-64 years), and older (65+ years) age groups.</p><p><strong>Results: </strong>Younger and middle-age individuals accounted for 142 of 200 (71%) of PNP and 995 of 1100 (90.5%) of NNP patients. Significant age-related differences in the frequencies of comorbidities and abnormal neurologic findings demonstrated higher prevalence in older patients. Conversely, 10 months from COVID-19 onset, we found significant age-related differences in Neuro-PASC symptoms indicating lower prevalence, and therefore, symptom burden, in older individuals. Moreover, there were significant age-related differences in subjective impression of fatigue (median [interquartile range (IQR)] patient-reported outcomes measurement information system [PROMIS] score: younger 64 [57-69], middle-age 63 [57-68], older 60.5 [50.8-68.3]; p = 0.04) and sleep disturbance (median [IQR] PROMIS score: younger 57 [51-63], middle-age 56 [53-63], older 54 [46.8-58]; p = 0.002) in the NNP group, commensurate with higher impairment in quality of life (QoL) among younger patients. Finally, there were significant age-related differences in objective executive function (median [IQR] National Institutes of Health [NIH] toolbox score: younger 48 [35-63], middle-age 49 [38-63], older 54.5 [45-66.3]; p = 0.01), and working memory (median [IQR] NIH toolbox score: younger 47 [40-53], middle-age 50 [44-57], older 48 [43-58]; p = 0.0002) in NNP patients, with the worst performance coming from the younger group.</p><p><strong>Interpretation: </strong>Younger and middle-age individuals are disproportionally affected by Neuro-PASC regardless of acute COVID-19 severity. Although older people more frequently have abnormal neurologic findings and comorbidities, younger and middle-age patients suffer from a higher burden of Neuro-PASC symptoms and cognitive dysfunction contributing to decreased QoL. Neuro-PASC principally affects adults in their prime, contributing to profound public health and socioeconomic impacts warranting dedicated resources for prevention, diagnosis and interventions. ANN NEUROL 2025;97:369-383.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"369-383"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilaterally Symmetrical Globus Pallidus Infarction.","authors":"Lizhang Chen, Jing Yang, Jinmei Li, Li He","doi":"10.1002/ana.27090","DOIUrl":"10.1002/ana.27090","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"254-255"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453942","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":"A Prospective Multicenter Analysis of Mobile Stroke Unit Cost-Effectiveness.","authors":"Suja S Rajan, Jose-Miguel Yamal, Mengxi Wang, Jeffrey L Saver, Asha P Jacob, Nicole R Gonzales, Nneka Ifejika, Stephanie A Parker, Christopher Ganey, Michael O Gonzalez, David R Lairson, Patti L Bratina, William J Jones, Jason S Mackey, Mackenzie P Lerario, Babak B Navi, Ann W Alexandrov, Andrei Alexandrov, May Nour, Ilana Spokoyny, Ritvij Bowry, Alexandra L Czap, James C Grotta","doi":"10.1002/ana.27105","DOIUrl":"10.1002/ana.27105","url":null,"abstract":"<p><strong>Objective: </strong>Given the high disease and cost burden of ischemic stroke, evaluating the clinical efficacy and cost-effectiveness of new approaches to prevent and treat ischemic stroke is critical. Effective ischemic stroke management depends on timely administration of thrombolytics after stroke onset. This study evaluates the cost-effectiveness associated with the use of mobile stroke units (MSUs) to expedite tissue plasminogen activator (tPA) administration, as compared with standard management through emergency medical services (EMS).</p><p><strong>Methods: </strong>This study is a prospective, multicenter, alternating-week, cluster-controlled trial of MSU versus EMS. One-year and life-time cost-effectiveness analyses, using the incremental cost-effectiveness ratio (ICER) method, were performed from the perspective of CMS's Medicare. Quality-adjusted life years (QALYs) estimated using patient-reported EQ-5D-5L data were used as the effectiveness measure. Health care utilizations were converted to costs using average national Medicare reimbursements. ICERs excluding patients with pre-existing disability, and limited to stroke-related costs were also calculated.</p><p><strong>Results: </strong>The first-year ICER for all tPA-eligible patients using total cost differences between MSU and EMS groups was $238,873/QALY; for patients without pre-existing disability was $61,199/QALY. The lifetime ICERs for all tPA-eligible patients and for those without pre-existing disability were $94,710 and $31,259/QALY, respectively. All ICERs were lower when restricted to stroke-related costs and were highly dependent on the number of patients treated per year in an MSU.</p><p><strong>Interpretation: </strong>MSUs' cost-effectiveness is borderline if we consider total first-year costs and outcomes in all tPA-eligible patients. MSUs are cost-effective to highly cost-effective when calculations are based on patients without pre-existing disability, patients' lifetime horizon, stroke-related costs, and more patients treated per year in an MSU. ANN NEUROL 2025;97:209-221.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"209-221"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764605","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":"RNA Binding Protein Dysfunction Links Smoldering/Slowly Expanding Lesions to Neurodegeneration in Multiple Sclerosis.","authors":"Miranda L Messmer, Hannah E Salapa, Bogdan F Popescu, Michael C Levin","doi":"10.1002/ana.27114","DOIUrl":"10.1002/ana.27114","url":null,"abstract":"<p><strong>Objective: </strong>Despite the advances in treatments for multiple sclerosis (MS), unremitting neurodegeneration continues to drive disability and disease progression. Smoldering/slowly expanding lesions (SELs) and dysfunction of the RNA binding protein (RBP) heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) are pathologic hallmarks of MS cortex and intricately tied to disability and neurodegeneration, respectively. We hypothesized that neuronal hnRNP A1 dysfunction contributes to neurodegeneration and is exacerbated by smoldering/SELs in progressive MS.</p><p><strong>Methods: </strong>Neuronal hnRNP A1 pathology (nucleocytoplasmic mislocalization of hnRNP A1) was examined in healthy control and MS brains using immunohistochemistry. MS cases were stratified by severity of hnRNP A1 pathology to examine the link between RBP dysfunction, demyelination, and neurodegeneration.</p><p><strong>Results: </strong>We found that smoldering/SELs were only present within a subset of MS tissues characterized by elevated neuronal hnRNP A1 pathology (MS-A1^high) in adjacent cortical gray matter. In contrast to healthy controls and MS with low hnRNP A1 pathology (MS-A1^low), MS-A1^high showed elevated markers of neurodegeneration, including neuronal loss and injury, brain atrophy, axonal loss, and axon degeneration. Additionally, we discovered a subpopulation of morphologically intact neurons lacking expression of NeuN, a neuron-specific RBP, in cortical projection neurons in MS-A1^high cases.</p><p><strong>Interpretation: </strong>hnRNP A1 dysfunction contributes to neurodegeneration and may be exacerbated by smoldering/SELs in progressive MS. The discovery of NeuN-negative neurons suggests that some cortical neurons may only be injured and not lost. By characterizing RBP pathology in MS cortex, this study has important implications for understanding the pathogenic mechanisms driving neurodegeneration, the substrate of disability and disease progression. ANN NEUROL 2025;97:313-328.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"313-328"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453965","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}