JAMA Neurology
本篇文献由机器智能翻译
The Most Difficult Question in a Cognitive Disorders Clinic
认知障碍诊所中最困难的问题
Neurocognitive disorders, commonly known as dementia, pose a significant diagnostic challenge in a bustling neurology clinic. The process of diagnosing an individual with dementia is multifaceted, and an individual’s journey to receive a definitive diagnosis is intricate. This assertion holds particular significance for people living in low- to middle-income countries who are affected by dementia, as the expenses associated with diagnostic assessments, albeit very low, remain unaffordable for caregivers. While it is common for a significant portion of individuals to be inaccurately identified as experiencing typical age-related changes, a subset of individuals may be erroneously diagnosed with psychiatric disorders, while a few others may be unnecessarily diagnosed with dementia at the initial phase of the illness, as evident by their numerous prescriptions of a combination of medications.
神经认知障碍,通常称为痴呆症,在繁忙的神经病学诊所中构成了重大的诊断挑战。诊断患有痴呆症的个体的过程是多方面的,并且个体接受明确诊断的旅程是错综复杂的。这一论断对生活在受痴呆症影响的中低收入国家的人特别重要,因为与诊断评估相关的费用虽然非常低,但护理人员仍然负担不起。虽然很大一部分人被不准确地识别为经历典型的年龄相关变化是很常见的,但一部分人可能被错误地诊断为精神疾病,而其他一些人可能在疾病的初始阶段被不必要地诊断为痴呆症。从他们众多的药物组合处方中可以看出。
REF: Arshad F, Alladi S. The Most Difficult Question in a Cognitive Disorders Clinic. JAMA Neurol. 2024;81(6):577-578. doi:10.1001/jamaneurol.2024.0143 PMID: 38497949
Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer DiseaseThe DIAN-TU-001 Randomized Clinical Trial
Gantenerumab或Solanezumab对显性遗传性阿尔茨海默病的下游生物标志物作用DIAN-TU-001随机临床试验
Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD). To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment. This randomized clinical trial supports the importance of fibrillar amyloid reduction in multiple AD-related processes of neuroinflammation and neurodegeneration in CSF and plasma in DIAD. Additional studies of antiaggregated amyloid therapies in sporadic AD and DIAD are needed to determine the utility of nonamyloid biomarkers in determining disease modification.
在显性遗传性阿尔茨海默病 (DIAD) 中,针对纤维状或可溶性单体淀粉样肽的抗淀粉样蛋白剂对脑脊液 (CSF) 和血浆中下游生物标志物的影响在很大程度上是未知的。研究接受抗淀粉样蛋白治疗的DIAD患者突触功能障碍、神经炎症和神经变性的纵向生物标志物变化。这项随机临床试验支持纤维状淀粉样蛋白减少在DIAD中CSF和血浆中与AD相关的神经炎症和神经变性的多个AD相关过程中的重要性。需要在散发性AD和DIAD中进行抗聚集淀粉样蛋白疗法的其他研究,以确定非淀粉样蛋白生物标志物在确定疾病修饰中的效用。
REF: Wagemann O, Liu H, Wang G, et al. Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial. JAMA Neurol. 2024;81(6):582-593. doi:10.1001/jamaneurol.2024.0991IF: 20.4 Q1 PMID: 38683602
Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic StrokeA Randomized Clinical Trial
替罗非班对急性缺血性卒中患者神经功能恶化的影响随机临床试验
Evidence supports using antiplatelet therapy in patients with acute ischemic stroke. However, neurological deterioration remains common under the currently recommended antiplatelet regimen, leading to poor clinical outcomes. To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin. In patients with noncardioembolic stroke who were seen within 24 hours of symptom onset, tirofiban decreased the risk of early neurological deterioration but did not increase the risk of symptomatic intracerebral hemorrhage or systematic bleeding.
证据支持在急性缺血性卒中患者中使用抗血小板治疗。然而,在目前推荐的抗血小板治疗方案下,神经功能恶化仍然很常见,导致不良的临床结果。确定与口服阿司匹林相比,在卒中发作24小时内静脉注射替罗非班是否可预防急性非心源性卒中患者的早期神经功能恶化。在症状发作24小时内发现的非心源性卒中患者中,替罗非班降低了早期神经功能恶化的风险,但没有增加症状性脑出血或系统性出血的风险。
REF: Zhao W, Li S, Li C, et al. Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial [published correction appears in JAMA Neurol. 2024 Jul 1. doi: 10.1001/jamaneurol.2024.2195]. JAMA Neurol. 2024;81(6):594-602. doi:10.1001/jamaneurol.2024.0868 PMID: 38648030
Ghrelin for Neuroprotection in Post–Cardiac Arrest Coma:A Randomized Clinical Trial
Ghrelin对心脏骤停后昏迷的神经保护作用: 一项随机临床试验
Out-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human study populations. To determine safety and potential efficacy of intravenous acyl-ghrelin to improve neurological outcome in patients in a coma after cardiac arrest. In patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence.
在过去的几十年中,院外心脏骤停的存活率显着提高,但神经系统结果仅略有改善。尽管对涉及心脏骤停后昏迷患者的20多种神经保护策略进行了研究,但尚无明确的疗效证据; 然而,在心脏骤停的实验模型中,用酰基生长素释放肽治疗已显示出改善的功能和组织学脑恢复,并且在各种人类研究人群中是安全的。确定静脉注射酰基生长素改善心脏骤停后昏迷患者神经系统预后的安全性和潜在疗效。在心脏骤停后昏迷的患者中,使用酰基生长素释放肽的静脉治疗是安全的,并且可能有效改善神经系统结果。3期试验需要确凿证据。
REF: Nutma S, Beishuizen A, van den Bergh WM, et al. Ghrelin for Neuroprotection in Post-Cardiac Arrest Coma: A Randomized Clinical Trial. JAMA Neurol. 2024;81(6):603-610. doi:10.1001/jamaneurol.2024.1088 PMID: 38709502
Association of New-Onset Seizures With SARS-CoV-2 VaccinesA Systematic Review and Meta-Analysis of Randomized Clinical Trials
新发癫痫与SARS-CoV-2疫苗的关联随机临床试验的系统评价和荟萃分析
Seizures have been reported as an adverse effect of the SARS-CoV-2 vaccine. However, no study has answered the question of whether there is any association between seizures in the general population and COVID-19 vaccination. To evaluate the seizure incidence among SARS-CoV-2 vaccine recipients compared with those who received a placebo. According to this systematic review and meta-analysis, there was no statistically significant difference in the risk of new-onset seizure incidence between vaccinated individuals and placebo recipients.
据报道,癫痫发作是SARS-CoV-2疫苗的不利影响。然而,没有研究回答一般人群的癫痫发作与新型冠状病毒肺炎疫苗接种之间是否存在任何关联的问题。评估SARS-CoV-2疫苗接种者与安慰剂接种者的癫痫发作发生率。根据这项系统评价和荟萃分析,接种疫苗的个体和安慰剂接受者之间新发癫痫发作的风险没有统计学上的显着差异。
REF: Rafati A, Jameie M, Amanollahi M, et al. Association of New-Onset Seizures With SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. JAMA Neurol. 2024;81(6):611-618. doi:10.1001/jamaneurol.2024.0967 PMID: 38683573
Clinicopathologic Heterogeneity and Glial Activation Patterns in Alzheimer Disease
阿尔茨海默病的临床病理异质性和神经胶质激活模式
Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement. To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy. Findings show that AD heterogeneity exists along a continuum of corticolimbic tangle distribution. Reduced CD68 burden may signify an underappreciated association between tau accumulation and microglia/macrophages activation that should be considered in personalized therapy for immune dysregulation.
与阿尔茨海默病 (AD) 的临床异质性相关的因素存在于假设与缠结分布相关的连续体中,并且与理解治疗进展中的神经胶质激活考虑有关。使用皮质边缘指数 (CLix) 沿着定量连续体检查AD疾病异质性的临床病理和神经影像学特征,以解释尸检中发现的空间分布缠结的个性。研究结果表明,AD异质性沿着皮质边缘缠结分布的连续体存在。减少的CD68负荷可能意味着tau积累与小胶质细胞/巨噬细胞活化之间的关联不足,应在免疫失调的个性化治疗中考虑。
REF: Kouri N, Frankenhauser I, Peng Z, et al. Clinicopathologic Heterogeneity and Glial Activation Patterns in Alzheimer Disease. JAMA Neurol. 2024;81(6):619-629. doi:10.1001/jamaneurol.2024.0784 PMID: 38619853
Antithrombotic Treatment for Cervical Artery DissectionA Systematic Review and Individual Patient Data Meta-Analysis
颈部动脉夹层的抗血栓治疗系统评价和个体患者数据的Meta分析
Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients. To perform an individual patient data meta-analysis of randomized clinical trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection. This individual patient data meta-analysis of 2 currently available randomized clinical trial data found no significant difference between anticoagulants and antiplatelets in preventing early recurrent events.
颈部动脉夹层是年轻人中风的最常见原因。迄今为止,尚无确凿证据表明应使用哪种抗血栓疗法来治疗患者。对比较抗凝药和抗血小板药物预防颈部动脉夹层术后卒中的随机临床试验进行个体患者数据荟萃分析。对2个当前可用的随机临床试验数据进行的个体患者数据荟萃分析发现,抗凝剂和抗血小板药在预防早期复发事件方面没有显着差异。
REF: Kaufmann JE, Harshfield EL, Gensicke H, et al. Antithrombotic Treatment for Cervical Artery Dissection: A Systematic Review and Individual Patient Data Meta-Analysis. JAMA Neurol. 2024;81(6):630-637. doi:10.1001/jamaneurol.2024.1141 PMID: 38739383
Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease
分期双侧MRI引导下聚焦超声丘脑底切开术治疗帕金森病
Unilateral magnetic resonance imaging (MRI)-guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored. To assess the safety and effectiveness of staged bilateral FUS-STN to treat PD. Findings of this pilot study suggest that staged bilateral FUS-STN was safe and effective for the treatment of PD, although mild but persistent speech-related adverse events were observed among a small number of patients.
单侧磁共振成像 (MRI) 引导的聚焦超声丘脑底切开术 (FUS-STN) 可改善不对称帕金森病 (PD) 患者的主要运动特征。双边fus-stn的可行性尚未探索。评估分期双侧fus-stn治疗PD的安全性和有效性。这项初步研究的结果表明,分期双侧fus-stn治疗PD是安全有效的,尽管在少数患者中观察到轻度但持续的言语相关不良事件。
REF: Martínez-Fernández R, Natera-Villalba E, Rodríguez-Rojas R, et al. Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease. JAMA Neurol. 2024;81(6):638-644. doi:10.1001/jamaneurol.2024.1220 PMID: 38739377
Progress in Pharmacologic Management of Neuropsychiatric Syndromes in Neurodegenerative DisordersA Review
神经退行性疾病中神经精神综合征的药物治疗进展综述
Neuropsychiatric syndromes (NPSs) are common in neurodegenerative disorders (NDDs); compromise the quality of life of patients and their care partners; and are associated with faster disease progression, earlier need for nursing home care, and poorer quality of life. Advances in translational pharmacology, clinical trial design and conduct, and understanding of the pathobiology of NDDs are bringing new therapies to clinical care. Detection and characterization of NPSs in patients with NDDs is the foundation for excellent care. New definitions for NPSs in NDDs may inform choices regarding clinical trial populations and translate into clinical practice. Psychosocial and pharmacologic therapies may reduce behavioral symptoms and improve quality of life for patients and caregivers. Approved agents may establish regulatory precedents, demonstrate successful trial strategies, and provide the foundation for further advances in treatment development.
神经精神综合征 (NPSs) 在神经退行性疾病 (ndd) 中很常见; 损害患者及其护理伙伴的生活质量; 并且与更快的疾病进展,更早需要疗养院护理以及较差的生活质量有关。转化药理学,临床试验设计和实施以及对ndd病理生物学的理解的进步正在为临床护理带来新的疗法。NDDs患者NPSs的检测和表征是优质护理的基础。NDDs中nps的新定义可能会为临床试验人群的选择提供信息,并转化为临床实践。社会心理和药物治疗可以减轻行为症状,改善患者和护理人员的生活质量。批准的药物可以建立监管先例,证明成功的试验策略,并为治疗开发的进一步进展奠定基础。
REF: Cummings J, Lanctot K, Grossberg G, Ballard C. Progress in Pharmacologic Management of Neuropsychiatric Syndromes in Neurodegenerative Disorders: A Review. JAMA Neurol. 2024;81(6):645-653. doi:10.1001/jamaneurol.2024.0586 PMID: 38558015
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