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Trends in Gender, Racial, and Ethnic Representation Among US Neurology Faculty. 美国神经病学教职员工的性别、种族和民族代表性趋势。
IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-18 DOI: 10.1001/jamaneurol.2024.3909
Chia-Chen Tsai, Chen Hu, Jeffrey Ding, Esther Bui, Aleksandra Pikula, Thalia S Field, Sabeen Tiwana, Javed Siddiqi, Faisal Khosa
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引用次数: 0
Amyloid-Related Imaging Abnormalities in Clinical Trials of Gantenerumab in Early Alzheimer Disease. 甘特宁单抗治疗早期阿尔茨海默病临床试验中与淀粉样蛋白相关的成像异常。
IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-18 DOI: 10.1001/jamaneurol.2024.3937
Stephen Salloway, Jakub Wojtowicz, Nicola Voyle, Christopher A Lane, Gregory Klein, Marco Lyons, Simona Rossomanno, Francesca Mazzo, Szofia Bullain, Frederik Barkhof, Tobias Bittner, Andres Schneider, Michael Grundman, Roxana Aldea, Mercè Boada, Janice Smith, Rachelle Doody
<p><strong>Importance: </strong>Data from 2 phase 3 studies of gantenerumab, GRADUATE I/II, and their open-label extensions represent a resource to further characterize amyloid-related imaging abnormalities (ARIA), including long-term sequelae.</p><p><strong>Objectives: </strong>To describe the characteristics of ARIA and risk factors and clinical consequences of ARIA-edema (ARIA-E).</p><p><strong>Design, setting, and participants: </strong>Secondary data collection from the GRADUATE I/II phase 3 randomized, double-blind, placebo-controlled, 116-week parallel-group studies and their open-label extensions, including PostGraduate, with up to 210 (mean, 125) weeks of total gantenerumab treatment were conducted between 2018 and 2023. The study included multicenter trials at 288 sites across 30 countries. GRADUATE I/II enrolled 985 and 980 participants, respectively, with early symptomatic Alzheimer disease (AD) and amyloid-beta (Aβ) pathology who were aged 50 to 90 years. PostGraduate enrolled 1382 participants (671 previously randomized to gantenerumab). Data were analyzed from November 2, 2022, to October 10, 2023.</p><p><strong>Interventions: </strong>GRADUATE I/II participants were randomized 1:1 to gantenerumab or placebo. Nine-month uptitration was used to mitigate ARIA risk.</p><p><strong>Main outcomes and measures: </strong>Postbaseline safety monitoring, including brain magnetic resonance imaging (MRI) findings, and adverse events and cognitive assessments.</p><p><strong>Results: </strong>The safety-evaluable MRI population of GRADUATE I/II comprised 1939 participants (mean age, 71.7 years; 1105 female [57.0%]). Severity of AD-related Aβ neuropathology (lower cerebrospinal fluid [CSF] Aβ42, hazard ratio [HR] for CSF Aβ42: 0.4; 95% CI, 0.2-0.7) and comorbid cerebrovascular pathology (Fazekas score: HR, 1.6; 95% CI, 1.3-2.0; total superficial siderosis count: HR, 1.9; 95% CI, 1.3-2.6; total microhemorrhage count: HR, 1.3; 95% CI, 1.0-1.5) may be important baseline risk factors for ARIA-E, in addition to apolipoprotein E (APOE) ε4 status (APOE ε4 heterozygous carrier: HR, 2.0; 95% CI, 1.4-2.8 and APOE ε4 homozygous carrier: HR, 4.7; 95% CI, 3.2-6.7). At the group level, ARIA-E did not impact long-term cognitive and functional performance (relative difference in adjusted means for Clinical Dementia Rating-Sum of Boxes was -9% in pooled GRADUATE analysis at week 116 and when censored at first ARIA-E). While taking gantenerumab, ARIA-E and ARIA-hemosiderin occurred in 24.9% (247 of 993) and 22.9% (227 of 993) participants, respectively; first ARIA-E occurred by week 64 in 86.2% (213 of 247) of participants with ARIA-E. Narratives are provided for all serious symptomatic ARIA-E cases.</p><p><strong>Conclusions and relevance: </strong>These results show that in addition to APOE ε4 allele count, severity of Aβ neuropathology and comorbid cerebrovascular pathology may be relevant for clinicians prescribing anti-Aβ monoclonal antibodies for early AD an
重要性:两项甘特宁单抗3期研究(GRADUATE I/II)及其开放标签延伸研究的数据是进一步描述淀粉样蛋白相关成像异常(ARIA)特征(包括长期后遗症)的资源:描述ARIA的特征以及ARIA-水肿(ARIA-E)的风险因素和临床后果:2018年至2023年期间,从GRADUATE I/II三期随机、双盲、安慰剂对照、116周平行组研究及其开放标签扩展研究(包括PostGraduate)中收集二次数据,甘特鲁单抗总治疗时间长达210周(平均125周)。研究包括在 30 个国家的 288 个研究机构进行的多中心试验。GRADUATE I/II分别招募了985名和980名年龄在50至90岁之间、患有早期症状性阿尔茨海默病(AD)和淀粉样蛋白-β(Aβ)病理的参与者。PostGraduate招募了1382名参与者(其中671人之前随机接受过甘特奈鲁单抗治疗)。数据分析时间为2022年11月2日至2023年10月10日:GRADUATE I/II 参与者按 1:1 随机分配到 gantenerumab 或安慰剂。主要结果和测量指标:基线后安全性监测,包括脑磁共振成像(MRI)结果、不良事件和认知评估:GRADUATE I/II 的 MRI 安全有效人群包括 1939 名参与者(平均年龄 71.7 岁;1105 名女性 [57.0%])。AD相关Aβ神经病理学的严重程度(较低的脑脊液[CSF] Aβ42,CSF Aβ42的危险比[HR]:0.4;95% CI,0.2-0.7)和合并脑血管病变的严重程度(Fazekas评分:HR,1.6;95% CI,1.3-2.0;表层蛛网膜总计数:HR,1.9;95% CI,1.3-2.6;微出血总数:除了载脂蛋白 E(APOE)ε4 状态(APOE ε4杂合子携带者:HR,2.0;95% CI,1.4-2.8;APOE ε4同合子携带者:HR,4.7;95% CI,3.2-6.7)外,HR,1.3;95% CI,1.0-1.5)也可能是 ARIA-E 的重要基线风险因素。在群体水平上,ARIA-E对长期认知和功能表现没有影响(在第116周的GRADUATE汇总分析中,临床痴呆评级-方框总和调整后平均值的相对差异为-9%,在首次ARIA-E时进行删减)。在服用甘特纳单抗期间,分别有24.9%(993人中有247人)和22.9%(993人中有227人)的参与者出现ARIA-E和ARIA-血色素;86.2%(247人中有213人)的ARIA-E参与者在第64周之前出现首次ARIA-E。所有有严重症状的 ARIA-E 病例都有叙述:这些结果表明,除了APOE ε4等位基因数外,Aβ神经病理学和合并脑血管病学的严重程度可能与临床医生开具抗Aβ单克隆抗体治疗早期AD处方和制定个体化安全监测计划有关。建议在其他抗Aβ单克隆抗体中评估这些风险因素:试验注册:ClinicalTrials.gov Identifiers:NCT03444870、NCT03443973、NCT04374253。
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引用次数: 0
Clinical Presentation, Investigation Findings, and Outcomes of IgG4-Related Pachymeningitis: A Systematic Review. IgG4 相关性脑脊髓膜炎的临床表现、检查结果和预后:系统回顾
IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-18 DOI: 10.1001/jamaneurol.2024.3947
Sara Terrim, João Vitor Mahler, Flávio Vieira Marques Filho, Leandro Tavares Lucato, Henrique Mayrink Giardini, Tarso Adoni, Guilherme Diogo Silva

Importance: Immunoglobulin G4 (IgG4)-related disease is an increasingly recognized fibroinflammatory condition that can involve multiple organs, including the pachymeninges. The understanding of IgG4-related pachymeningitis (IgG4-RP) remains limited because of its rarity and the predominance of knowledge derived from case reports and case series.

Objective: To systematically review and synthesize the clinical presentation, investigation findings, and prognosis of IgG4-RP to better understand its diagnosis and management.

Evidence review: A comprehensive systematic review was conducted following guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed/MEDLINE, Embase, and Scopus were searched from their inception until May 30, 2023, using terms related to IgG4-related disease and pachymeningitis without language or publication restrictions. Case reports and series that met the 2020 Revised Comprehensive Diagnostic Criteria or the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria were included. Data on clinical presentations, investigation findings, and treatment outcomes were extracted and summarized.

Findings: A total of 148 case reports contributed data from 208 patients. Their median (IQR) age was 52 (39-62) years; 132 patients were male (63.5%) and 76 female (36.5%). Headache and cranial nerve dysfunctions were the most common neurological manifestations. Systemic involvement was identified in nearly half of the patients. Diagnostic imaging often showed preferential involvement of cavernous sinus and middle fossa. Laboratory results highlighted elevated serum IgG4 levels in 97 of 147 patients (65%) of patients and cerebrospinal fluid pleocytosis in 43 of 82 patients (52%). Storiform fibrosis or obliterating phlebitis were uncommon pathological findings. Mortality was below 1% (1/134; 0.7%), but only a third of patients presented complete clinical improvement, and the recurrence rate was 60 patients (40%) in a median (IQR) follow-up time of 9 (1-20) months. Glucocorticoids were the most commonly prescribed treatment, in 143 of 169 patients (85%); rituximab was prescribed as maintenance therapy in 53 of 169 patients (31%).

Conclusions and relevance: IgG4-RP commonly presents with headaches and cranial nerve dysfunction, posing diagnostic challenges due to the significant absence of systemic manifestations, low IgG4 serum levels, and atypical pathological findings. Current treatment outcomes are limited by incomplete recovery and frequent relapses underscoring the necessity for new treatment strategies.

重要性:与免疫球蛋白 G4 (IgG4) 相关的疾病是一种日益得到认可的纤维炎症,可累及包括咽鼓管在内的多个器官。由于 IgG4 相关性咽鼓管炎(IgG4-RP)非常罕见,且主要知识来自病例报告和系列病例,因此人们对该病的了解仍然有限:系统回顾和总结 IgG4-RP 的临床表现、检查结果和预后,以更好地了解其诊断和治疗:根据《系统综述和荟萃分析首选报告项目》的指导原则进行了全面的系统综述。从 PubMed/MEDLINE、Embase 和 Scopus 开始至 2023 年 5 月 30 日,使用与 IgG4 相关疾病和帕奇脑膜炎相关的术语进行检索,无语言或出版限制。符合2020年修订的综合诊断标准或2019年美国风湿病学会/欧洲抗风湿病联盟分类标准的病例报告和系列研究均被纳入。提取并总结了有关临床表现、检查结果和治疗效果的数据:共有 148 份病例报告提供了 208 名患者的数据。他们的中位(IQR)年龄为 52(39-62)岁;132 名患者为男性(63.5%),76 名患者为女性(36.5%)。头痛和颅神经功能障碍是最常见的神经系统表现。近一半的患者可发现全身受累。影像诊断通常显示海绵窦和中窝优先受累。实验室结果显示,147 例患者中有 97 例(65%)血清 IgG4 水平升高,82 例患者中有 43 例(52%)脑脊液多细胞增多。茎状纤维化或闭塞性静脉炎是不常见的病理结果。死亡率低于1%(1/134;0.7%),但只有三分之一的患者临床症状完全好转,在中位(IQR)为9(1-20)个月的随访期间,复发率为60例(40%)。糖皮质激素是最常用的处方治疗药物,169 例患者中有 143 例(85%)使用了糖皮质激素;169 例患者中有 53 例(31%)使用了利妥昔单抗作为维持治疗药物:IgG4-RP通常表现为头痛和颅神经功能障碍,由于明显缺乏全身表现、IgG4血清水平低和病理结果不典型,给诊断带来了挑战。目前的治疗效果受到不完全康复和频繁复发的限制,这凸显了新治疗策略的必要性。
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引用次数: 0
AI Devices in Neurology-Moving From Diagnosis to Prognosis. 神经病学中的人工智能设备--从诊断到预后。
IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-18 DOI: 10.1001/jamaneurol.2024.3835
James M Hillis, Edward R Scheffer Cliff, Kerstin N Vokinger
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引用次数: 0
Gantenerumab in Dominantly Inherited Alzheimer Disease-Reply. 甘特宁单抗治疗显性遗传性阿尔茨海默病--回复。
IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-11 DOI: 10.1001/jamaneurol.2024.3828
Olivia Wagemann, Eric McDade, Randall J Bateman
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引用次数: 0
Gantenerumab in Dominantly Inherited Alzheimer Disease. 甘特宁单抗治疗显性遗传性阿尔茨海默病
IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-11 DOI: 10.1001/jamaneurol.2024.3825
Nunzio Pomara, Bruno Pietro Imbimbo
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引用次数: 0
Circadian Motor Improvement in MS and Core Body Temperature Dipping. 多发性硬化症的昼夜节律运动改善与核心体温下降。
IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-09-01 DOI: 10.1001/jamaneurol.2024.1812
Milan Nigam, Alain Créange, Smaranda Leu-Semenescu
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引用次数: 0
Cerebral Amyloid Angiopathy and Nontraumatic Subdural Hemorrhage. 脑淀粉样血管病和非外伤性硬膜下出血。
IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 DOI: 10.1001/jamaneurol.2024.1595
Francesco Bax, Steven M Greenberg
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引用次数: 0
Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy. 治疗高血压的血管紧张素受体阻滞剂与癫痫风险。
IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 DOI: 10.1001/jamaneurol.2024.1714
Xuerong Wen, Marianne N Otoo, Jie Tang, Todd Brothers, Kristina E Ward, Nicole Asal, Kimford J Meador
<p><strong>Importance: </strong>Animal and human studies have suggested that the use of angiotensin receptor blockers (ARBs) may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, observational data from the US are lacking.</p><p><strong>Objective: </strong>To evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension.</p><p><strong>Design, setting, and participants: </strong>This retrospective cohort study used data from a national health administrative database from January 2010 to December 2017 with propensity score (PS) matching. The eligible cohort included privately insured individuals aged 18 years or older with diagnosis of primary hypertension and dispensed at least 1 ARB, angiotensin-converting enzyme inhibitor (ACEI), β-blocker, or calcium channel blocker (CCB) from 2010 to 2017. Patients with a diagnosis of epilepsy at or before the index date or dispensed an antiseizure medication 12 months before or 90 days after initiating the study medications were excluded. The data analysis for this project was conducted from April 2022 to April 2024.</p><p><strong>Exposures: </strong>Propensity scores were generated based on baseline covariates and used to match patients who received ARBs with those who received either ACEIs, β-blockers, CCBs, or a combination of these antihypertensive medications.</p><p><strong>Main outcomes and measures: </strong>Cox regression analyses were used to evaluate epilepsy incidence during follow-up comparing the ARB cohort with other antihypertensive classes. Subgroup and sensitivity analyses were conducted to examine the association between ARB use and epilepsy incidence in various subgroups.</p><p><strong>Results: </strong>Of 2 261 964 patients (mean [SD] age, 61.7 [13.9] years; 1 120 630 [49.5%] female) included, 309 978 received ARBs, 807 510 received ACEIs, 695 887 received β-blockers, and 448 589 received CCBs. Demographic and clinical characteristics differed across the 4 comparison groups prior to PS matching. Compared with ARB users, patients receiving ACEIs were predominantly male and had diabetes, CCB users were generally older (eg, >65 years), and β-blocker users had more comorbidities and concurrent medications. The 1:1 PS-matched subgroups included 619 858 patients for ARB vs ACEI, 619 828 patients for ARB vs β-blocker, and 601 002 patients for ARB vs CCB. Baseline characteristics were equally distributed between comparison groups after matching with propensity scores. Use of ARBs was associated with a decreased incidence of epilepsy compared with ACEIs (adjusted hazard ratio [aHR], 0.75; 95% CI, 0.58-0.96), β-blockers (aHR, 0.70; 95% CI, 0.54-0.90), and a combination of other antihypertensive classes (aHR, 0.72; 95% CI, 0.56-0.95). Subgroup analyses revealed a significant association between ARB use (primarily losartan) and epilepsy incidence in patients with no preexisting history of stro
重要性:动物和人体研究表明,与其他抗高血压药物相比,使用血管紧张素受体阻滞剂(ARB)可能与较低的癫痫发病风险有关。然而,目前还缺乏来自美国的观察性数据:目的:评估美国高血压患者亚群中使用 ARB 与癫痫发病率之间的关系:这项回顾性队列研究使用了 2010 年 1 月至 2017 年 12 月全国健康管理数据库中的数据,并进行了倾向得分(PS)匹配。符合条件的队列包括年龄在 18 岁或以上、诊断为原发性高血压且在 2010 年至 2017 年期间至少配发过一种 ARB、血管紧张素转换酶抑制剂(ACEI)、β-受体阻滞剂或钙通道阻滞剂(CCB)的私人投保者。不包括在指标日期或之前诊断为癫痫或在开始服用研究药物前 12 个月或之后 90 天内配发过抗癫痫药物的患者。本项目的数据分析时间为 2022 年 4 月至 2024 年 4 月:根据基线协变量生成倾向评分,用于将接受 ARBs 治疗的患者与接受 ACEIs、β-受体阻滞剂、CCBs 或这些降压药物组合治疗的患者进行匹配:采用Cox回归分析评估随访期间的癫痫发病率,并将ARB群组与其他抗高血压类药物进行比较。进行了亚组分析和敏感性分析,以研究不同亚组中使用 ARB 与癫痫发病率之间的关系:在纳入的 2 261 964 例患者中(平均 [SD] 年龄为 61.7 [13.9] 岁;女性 1 120 630 [49.5%]),309 978 例接受了 ARBs 治疗,807 510 例接受了 ACEIs 治疗,695 887 例接受了 β 受体阻滞剂治疗,448 589 例接受了 CCBs 治疗。在进行 PS 匹配之前,4 个对比组的人口统计学特征和临床特征各不相同。与 ARB 使用者相比,接受 ACEIs 的患者以男性和糖尿病患者为主,CCB 使用者一般年龄较大(例如,大于 65 岁),而 β 受体阻滞剂使用者有更多的合并症和并发症。1:1 PS 匹配亚组包括 619 858 例 ARB vs ACEI 患者、619 828 例 ARB vs β-受体阻滞剂患者和 601 002 例 ARB vs CCB 患者。经倾向评分匹配后,对比组之间的基线特征分布相同。与 ACEIs(调整后危险比 [aHR],0.75;95% CI,0.58-0.96)、β-受体阻滞剂(aHR,0.70;95% CI,0.54-0.90)和其他降压类药物组合(aHR,0.72;95% CI,0.56-0.95)相比,使用 ARBs 与癫痫发病率降低相关。亚组分析显示,在既往无中风或心血管疾病史的患者中,ARB(主要是洛沙坦)的使用与癫痫发病率之间存在显著关联:这项队列研究发现,在无中风或心血管疾病史的高血压患者中,与其他抗高血压药物相比,ARBs(主要是洛沙坦)与较低的癫痫发病率相关。有必要开展进一步的研究,如随机临床试验,以确认抗高血压药物的抗致痫性比较。
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引用次数: 0
Incorrect Nomenclature May Lead to Questionable Concepts. 不正确的命名可能会导致有疑问的概念。
IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 DOI: 10.1001/jamaneurol.2024.1660
Carsten A Wagner
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引用次数: 0
期刊
JAMA neurology
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