Annals of Neurology最新文献

{"title":"Carotid Stent Fracture","authors":"Ioana Maria Ion MD, Dimitri Renard MD","doi":"10.1002/ana.27127","DOIUrl":"10.1002/ana.27127","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"207-208"},"PeriodicalIF":8.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563591","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":"Longitudinal Magnetic Resonance Imaging in Asymptomatic C9orf72 Mutation Carriers Distinguishes Phenoconverters to Amyotrophic Lateral Sclerosis or Amyotrophic Lateral Sclerosis With Frontotemporal Dementia","authors":"Kevin van Veenhuijzen MD,&nbsp;Harold H.G. Tan MD,&nbsp;Abram D. Nitert MD,&nbsp;Michael A. van Es MD, PhD,&nbsp;Jan H. Veldink MD, PhD,&nbsp;Leonard H. van den Berg MD, PhD,&nbsp;Henk-Jan Westeneng MD, PhD","doi":"10.1002/ana.27116","DOIUrl":"10.1002/ana.27116","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We prospectively studied asymptomatic <i>C9orf72</i> mutation carriers, identifying those developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 56 asymptomatic family members (AFM) with a <i>C9orf72</i> mutation (AFM C9+), 132 non-carriers (AFM C9−), and 359 population-based controls. Using 3 T magnetic resonance imaging, we measured cortical thickness, gyrification, and subcortical volumes longitudinally. Linear mixed-effects models on non-converting AFM C9+ scans (n = 107) created a reference for these measurements, establishing individual atrophy patterns. Atrophy patterns from presymptomatic phenoconverters (n = 10 scans) served as a template for group comparisons and similarity assessments. Similarity with phenoconverters was quantified using Dice similarity coefficient (DSC) for cortical and Kullback–Leibler similarity (KLS) for subcortical measures. Using longitudinal similarity assessments, we predicted when participants would reach the average similarity level of phenoconverters at their first post-onset scan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five AFM C9+ converted to ALS or ALS-FTD. Up to 6 years before symptoms, these phenoconverters exhibited significant atrophy in frontal, temporal, parietal, and cingulate cortex, along with smaller thalamus, hippocampus, and amygdala compared to other AFM C9+. Some non-converted AFM C9+ had high DSC and KLS, approaching values of phenoconverters, whereas others, along with AFM C9− and controls, had lower values. At age 80, we predicted 27.9% (95% confidence interval, 13.2–40.1%) of AFM C9+ and no AFM C9− would reach the same DSC as phenoconverters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Distinctive atrophy patterns are visible years before symptom onset on presymptomatic scans of phenoconverters. Combining baseline and follow-up similarity measures may serve as a promising imaging biomarker for identifying those at risk of ALS or ALS-FTD. ANN NEUROL 2025;97:281–295</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 2","pages":"281-295"},"PeriodicalIF":8.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563593","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":"Minimally Invasive Surgery for Spontaneous Intracerebral Hemorrhage: Meta-Analysis of High-Quality Randomized Clinical Trials","authors":"Ahmed Alkhiri MBBS,&nbsp;Aser F. Alamri MBBS,&nbsp;Ahmed A. Almaghrabi MBBS,&nbsp;Fahad Alturki MBBS,&nbsp;Basil A. Alghamdi MBBS,&nbsp;Abdullah Alharbi MBBS,&nbsp;Hassan K. Salamatullah MBBS,&nbsp;Mohamed Alzawahmah MD,&nbsp;Faisal Al-Otaibi MD,&nbsp;Abdulrahman Y. Alturki MBBS,&nbsp;Dar Dowlatshahi MD, PhD,&nbsp;Andrew M. Demchuk MD,&nbsp;Wendy C. Ziai MD,&nbsp;Christopher P. Kellner MD,&nbsp;Adel Alhazzani MD,&nbsp;Fahad S. Al-Ajlan MD","doi":"10.1002/ana.27107","DOIUrl":"10.1002/ana.27107","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Spontaneous intracerebral hemorrhage (ICH) poses high mortality and morbidity rates with limited evidence-based therapeutic approaches. We aimed to evaluate the current evidence for the role of minimally invasive surgery (MIS) in the management of ICH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This systematic review and meta-analysis followed recommended guidelines and protocols. Medline, Embase, Scopus, and the Cochrane Library were searched from inception up to April 12, 2024. The inclusion was restricted to randomized clinical trials (RCTs) of high quality, ensuring they were not deemed to have a high risk of bias in any of the Cochrane risk of bias tool (RoB2) domains. Primary outcomes were good functional outcome (modified Rankin scale, 0–3) and mortality beyond 90 days. Secondary outcomes were early mortality within 30 days and rebleeding rates. We pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using random-effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fourteen high-quality RCTs were included. There were 3,027 patients with ICH (1,475 randomized to MIS, and 1,452 randomized to medical management or craniotomy). Of included patients, 1,899 (62.7%) were males. MIS resulted in higher odds of achieving long-term good functional outcome (OR, 1.51 [95% CI, 1.25–1.82]), lower odds of long-term mortality (OR, 0.72 [95% CI, 0.57–0.90]) and lower odds of early mortality (OR, 0.73 [95% CI, 0.56–0.95]). Rebleeding rates were similar (OR, 1.10 [95% CI, 0.55–2.19]). The treatment effect of MIS was consistent across multiple sensitivity and subgroup analyses, including individuals with deep ICH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This meta-analysis provides high-quality clinical trial evidence supporting the use of MIS as a primary treatment strategy in the management of ICH. ANN NEUROL 2025;97:185–194</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"185-194"},"PeriodicalIF":8.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542310","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":"Cost-Effectiveness of Endovascular Thrombectomy in Patients with Large Ischemic Stroke","authors":"Lan Gao PhD,&nbsp;Leonid Churilov PhD,&nbsp;Hannah Johns PhD,&nbsp;Deep Pujara MBBS,&nbsp;Ameer E. Hassan DO,&nbsp;Michael Abraham MD,&nbsp;Santiago Ortega-Gutierrez MD,&nbsp;Muhammad Shazam Hussain MD,&nbsp;Michael Chen MD,&nbsp;Spiros Blackburn MD,&nbsp;Clark W. Sitton MD,&nbsp;Florentina M. E. Pinckaers MD,&nbsp;Wim H. van Zwam MD,&nbsp;Georgios Tsivgoulis MD,&nbsp;Michael D. Hill MD,&nbsp;James C. Grotta MD,&nbsp;Scott Kasner MD,&nbsp;Marc Ribo MD,&nbsp;Bruce C Campbell PhD,&nbsp;Amrou Sarraj MD,&nbsp;For SELECT2 investigators","doi":"10.1002/ana.27119","DOIUrl":"10.1002/ana.27119","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 2","pages":"222-231"},"PeriodicalIF":8.1,"publicationDate":"2024-10-31","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":"Directional Subthalamic Deep Brain Stimulation Better Improves Gait and Balance Disorders in Parkinson's Disease Patients: A Randomized Controlled Study","authors":"Saoussen Cherif PhD,&nbsp;Nicolas Tempier,&nbsp;Mathieu Yeche,&nbsp;Gizem Temiz PhD,&nbsp;Julia Perrière,&nbsp;Marco Romanato PhD,&nbsp;Déborah Ziri PhD,&nbsp;Sara Fernandez-Vidal PhD,&nbsp;Elodie Hainque MD, PhD,&nbsp;David Maltête MD, PhD,&nbsp;Stéphane Derrey MD, PhD,&nbsp;Eric Bardinet PhD,&nbsp;Brian Lau PhD,&nbsp;Carine Karachi MD, PhD,&nbsp;Marie-Laure Welter MD, PhD","doi":"10.1002/ana.27099","DOIUrl":"10.1002/ana.27099","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the effects of directional subthalamic deep brain stimulation (STN-dDBS) on gait and balance disorders, including freezing of gait (FOG), in patients with advanced Parkinson's disease (PD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 10 participants who underwent STN-DBS and presented severe preoperative FOG, in a randomized, double-blind, crossover study. We used segmented DBS electrodes to investigate whether directing the predicted volume of tissue activated (VTA) to overlap the central STN preferentially improved gait and balance disorders compared to directional DBS applied in the more posterior STN (sensorimotor). We also assessed non-directional (ring-mode) STN-DBS. Our primary outcome was gait and balance control measured using instrumented gait recordings. Each patient had a pre-operative structural and diffusion-weighted imaging to model individual VTAs and to examine cortico-subthalamic connectivity. We used linear mixed-effects models to contrast the effects of central STN-dDBS, posterior STN-dDBS, and ring-mode STN-DBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Central STN-dDBS produced significantly better improvement in gait and balance control compared to posterior STN-dDBS (<i>p</i> = 0.027), with fewer FOG episodes (<i>p</i> &lt; 0.001). Conversely, ring-mode STN-DBS resulted in worsened postural control compared to central STN-dDBS (<i>p</i> = 0.009). The cortico-subthalamic connectivity with the STN VTAs involved mostly primary sensorimotor, premotor, and medial frontal cortices, with a higher overall cortico-STN connectivity with ring-mode STN-DBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Central STN-dDBS represents the best option to improve gait and balance disorders in PD patients, including FOG. Our findings raise the possibility of reprogramming STN-DBS toward the central area in selected patients with disabling FOG and/or postural instability after surgery. ANN NEUROL 2025;97:149–162</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"149-162"},"PeriodicalIF":8.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542309","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 of Seizure Control with Mortality, Cognition, and Function in People With Dementia","authors":"Ifrah Zawar MD, MS-CR,&nbsp;Mark Quigg MD, MSc,&nbsp;Soutik Ghosal PhD,&nbsp;Vineet Punia MD, MSc,&nbsp;Yamile Calle-Lopez MD,&nbsp;Carol Manning PhD,&nbsp;Jaideep Kapur MD, PhD","doi":"10.1002/ana.27125","DOIUrl":"10.1002/ana.27125","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The effects of seizure control on outcomes in persons with dementia (PWD) remain unclear. Our study aimed to investigate the impact of seizure control on mortality, function, cognition, and mood among PWD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This longitudinal, multicenter study is based on 39 Alzheimer's disease centers (ADCs) in the United States from September 2005 to December 2021. PWD were grouped by seizure status into recurrent (seizures in the past year), remote (prior seizures but none in the past year), and no seizures (controls). The primary outcome was all-cause mortality among seizure groups. We used Weibull survival analysis to assess the mortality risks by seizure status after adjusting for age, sex, education, race, ethnicity, hypertension, diabetes, hyperlipidemia, degree of cognitive impairment, dominant Alzheimer's disease (AD) mutation, brain trauma, stroke, Parkinson's disease, alcohol abuse, and depression. Cognition (Clinical Dementia Rating), function (physical dependence and nursing home residence), day-to-day activities (Functional Assessment Scores), and mood (Geriatric Depression Scale) were compared among seizure groups after adjusting for dementia duration and age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 26,501 participants, 374 (1.4%) had recurrent seizures and 510 (1.9%) had remote seizures. In multivariable survival analysis, recurrent seizures were associated with a higher mortality risk than remote and no seizures (adjusted hazard ratio [aHR], 95% confidence interval [95% CI]; recurrent aHR = 1.79, 95% CI = 1.51 to 2.12; remote aHR = 1.17, 95% CI = 0.98 to 1.38). Median time-to-death for recurrent, remote, and no seizures was 2.4, 4.0, and 4.7 years, respectively. People with recurrent seizures had worse cognition, day-to-day function, and physical dependence than those with remote seizures and controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>PWD with poorly controlled recurrent seizures have worse mortality, functional, and cognitive outcomes than PWD with remote and no seizures. These findings underscore the need for timely identification and management of ongoing seizures in PWD. ANN NEUROL 2025;97:358–368</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 2","pages":"358-368"},"PeriodicalIF":8.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542307","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":"Transmantle Vein Persistence in Adulthood","authors":"Marialuisa Zedde MD, FESO,&nbsp;Rosario Pascarella MD","doi":"10.1002/ana.27122","DOIUrl":"10.1002/ana.27122","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"205-206"},"PeriodicalIF":8.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520471","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 Novel Mouse Model for Cerebral Inflammatory Demyelination in X-Linked Adrenoleukodystrophy: Insights into Pathogenesis and Potential Therapeutic Targets","authors":"Ezzat Hashemi PhD,&nbsp;Isha N. Srivastava MD, PhD,&nbsp;Alejandro Aguirre MD,&nbsp;Ezra T. Yoseph BS,&nbsp;Esha Kaushal PhD,&nbsp;Avni Awani PhD,&nbsp;Jae K. Ryu PhD,&nbsp;Katerina Akassoglou PhD,&nbsp;Shahrzad Talebian MSc,&nbsp;Pauline Chu BS, HT (ASCP),&nbsp;Laura Pisani PhD,&nbsp;Patricia Musolino MD, PhD,&nbsp;Lawrence Steinman MD,&nbsp;Kristian Doyle PhD,&nbsp;William H. Robinson MD, PhD,&nbsp;Orr Sharpe MSc,&nbsp;Romain Cayrol MD, PhD,&nbsp;Paul J. Orchard MD,&nbsp;Troy Lund MD, PhD,&nbsp;Hannes Vogel MD,&nbsp;Max Lenail BS,&nbsp;May H. Han MD,&nbsp;Joshua L. Bonkowsky MD, PhD,&nbsp;Keith P. Van Haren MD","doi":"10.1002/ana.27117","DOIUrl":"10.1002/ana.27117","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>X-linked adrenoleukodystrophy (ALD) is caused by mutations in <i>ABCD1</i>, a peroxisomal gene. More than half of males with an <i>ABCD1</i> mutation develop inflammatory cerebral demyelination (cALD), but underlying mechanisms remain unknown and therapies are limited. We sought to develop and characterize a mouse model of cALD to facilitate study of disease mechanisms and therapy development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used immunoassays and immunohistochemistry to assess novel (interleukin 18 [IL-18]) and established molecular markers in cerebrospinal fluid (CSF) and postmortem brain tissue from cALD patients. We generated a cALD phenotype in <i>Abcd1-</i>knockout mice using a 2-hit method that combines cuprizone and experimental autoimmune encephalomyelitis models. We then used magnetic resonance imaging (MRI) and immunohistochemistry to assess the fidelity of cALD molecular markers in the mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Human and mouse cALD lesions shared histologic features of myelin phagocytosis, myelin loss, abundant microglial activation, T and B-cell infiltration, and astrogliosis. Compared to wild-type controls, <i>Abcd1</i>-knockout mice displayed more cerebral demyelination, blood–brain barrier disruption, and perivascular immune cell infiltration. This enhanced inflammatory response was associated with higher levels of fibrin deposition, oxidative stress, demyelination, and axonal injury. IL-18 immunoreactivity co-localized with perivascular monocytes/macrophages in both human and mouse brain tissue. In cALD patients, CSF IL-18 levels correlated with MRI lesion severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our results suggest loss of <i>Abcd1</i> function in mice predisposes to more severe blood–brain barrier disruption, cerebral inflammation driven by the infiltration of peripheral immune cells, demyelination, and axonal damage, replicating human cALD features. This novel mouse model could shed light on cALD mechanisms and accelerate cALD therapy development. ANN NEUROL 2025;97:296–312</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 2","pages":"296-312"},"PeriodicalIF":8.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520470","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":"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 MSc,&nbsp;Shishi Xu MD, PhD,&nbsp;Caroline Ingre MD, PhD,&nbsp;Rosa Luisa Potenza PhD,&nbsp;Christina Seitz PhD,&nbsp;Huazhen Yang MSc,&nbsp;Yu Zeng MSc,&nbsp;Huan Song MD, PhD,&nbsp;Fang Fang MD, PhD","doi":"10.1002/ana.27109","DOIUrl":"10.1002/ana.27109","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Body composition at early and middle age may be indicative of the risk of MND development. ANN NEUROL 2025;97:259–269</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 2","pages":"259-269"},"PeriodicalIF":8.1,"publicationDate":"2024-10-25","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":"Polygenic Landscape of Cryptogenic New-Onset Refractory Status Epilepticus: A Comprehensive Whole-Genome Sequencing Study","authors":"Yoonhyuk Jang,&nbsp;Sung Eun Hong,&nbsp;Soo Hyun Ahn,&nbsp;Su Yee Mon,&nbsp;Ji Hye You,&nbsp;Kon Chu,&nbsp;Sang Kun Lee,&nbsp;Murim Choi,&nbsp;Soon-Tae Lee","doi":"10.1002/ana.27100","DOIUrl":"10.1002/ana.27100","url":null,"abstract":"<p>Cryptogenic new-onset refractory status epilepticus (cNORSE) is a devastating condition with unclear pathogenesis. Here, we analyzed the genetic underprints of 31 cNORSE patients from an autoimmune encephalitis observational cohort through whole-genome sequencing. Compared to their controls, cNORSE patients exhibited elevated polygenic risk scores (PRS) for traits associated with autoimmune diseases. The individual PRS against these diseases were correlated with specific clinical phenotypes of cNORSE. The variants were enriched in genes expressed in the central nervous system and lymphocytes. These results suggest a shared genetic framework between cNORSE and other autoimmune/autoinflammatory diseases, and its involvement in the disease pathogenesis. ANN NEUROL 2024;96:1201–1208</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"1201-1208"},"PeriodicalIF":8.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491411","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}