Safety and efficacy of early versus delayed acetylsalicylic acid after surgery for spontaneous intracerebral haemorrhage in China (E-start): a prospective, multicentre, open-label, blinded-endpoint, randomised trial

中国自发性脑出血术后早期与延迟使用乙酰水杨酸的安全性和有效性 (e-start): 一项前瞻性、多中心、开放标签、盲法终点、随机试验

Patients with non-traumatic intracerebral haemorrhage have a substantial risk of major adverse cardiovascular and cerebrovascular events, including ischaemic stroke, after surgery. The optimal timing of antiplatelet therapy after surgery for spontaneous intracerebral haemorrhage in patients at high risk of postoperative ischaemic events has not been characterised. We aimed to investigate the safety and efficacy of early versus late initiation of antiplatelet therapy after surgery for spontaneous intracerebral haemorrhage. Starting acetylsalicylic acid on the third day after surgery for spontaneous intracerebral haemorrhage in Chinese patients at high risk of postoperative ischaemic events resulted in fewer postoperative ischaemic major cardiovascular, cerebrovascular, or peripheral vascular events than starting acetylsalicylic acid therapy at 30 days, with no increased risk of intracranial bleeding. Whether early initiation of acetylsalicylic acid therapy is safe and improves clinical outcomes for broader populations of patients with spontaneous intracerebral haemorrhage requires further research.

非创伤性脑内出血的患者在手术后发生主要不良心血管和脑血管事件的风险很大，包括缺血性卒中。对于术后缺血性事件高风险的自发性脑出血患者，术后抗血小板治疗的最佳时机尚未确定。我们的目的是研究自发性脑出血手术后早期和晚期开始抗血小板治疗的安全性和有效性。在术后缺血性事件高风险的中国患者中，自发性脑出血术后第三天开始使用乙酰水杨酸，与30天开始使用乙酰水杨酸相比，术后缺血性主要心血管、脑血管或外周血管事件较少，颅内出血风险没有增加。对于更广泛的自发性脑出血患者，早期开始乙酰水杨酸治疗是否安全并改善临床结局需要进一步研究。

REF: Liu Q, Mo S, Wu J, et al. Safety and efficacy of early versus delayed acetylsalicylic acid after surgery for spontaneous intracerebral haemorrhage in China (E-start): a prospective, multicentre, open-label, blinded-endpoint, randomised trial. Lancet Neurol. 2024;23(12):1195-1204. doi:10.1016/S1474-4422(24)00424-1 PMID: 39577920

Intravenous glibenclamide for cerebral oedema after large hemispheric stroke (CHARM): a phase 3, double-blind, placebo-controlled, randomised trial

静脉注射格列本脲治疗大半球卒中后脑水肿 (CHARM): 一项3期、双盲、安慰剂对照、随机试验

No treatment is available to prevent brain oedema, which can occur after a large hemispheric infarction. Glibenclamide has previously been shown to improve functional outcome and reduce neurological or oedema-related death in patients younger than 70 years who were at risk of brain oedema after an acute ischaemic stroke. We aimed to assess whether intravenous glibenclamide could improve functional outcome at 90 days in patients with large hemispheric infarction. Intravenous glibenclamide did not improve functional outcome in patients aged 18-70 years after large hemispheric infarction, although the trial was underpowered to make definitive conclusions because it was stopped early. Future prospective evaluation could be warranted to identify a possible benefit of intravenous glibenclamide in specific subgroups.

没有治疗方法可以预防大半球梗塞后可能发生的脑水肿。格列本脲先前已被证明可改善70岁以下急性缺血性卒中后有脑水肿风险的患者的功能结局并减少神经系统或水肿相关的死亡。我们旨在评估静脉注射格列本脲是否可以改善大脑半球大面积梗死患者90天的功能结局。静脉注射格列本脲不能改善大面积脑梗死后18-70岁患者的功能结局，尽管该试验因早期停止而不足以得出明确的结论。未来的前瞻性评估可能需要确定静脉注射格列本脲在特定亚组中的可能益处。

REF: Sheth KN, Albers GW, Saver JL, et al. Intravenous glibenclamide for cerebral oedema after large hemispheric stroke (CHARM): a phase 3, double-blind, placebo-controlled, randomised trial [published correction appears in Lancet Neurol. 2025 Jan;24(1):e1. doi: 10.1016/S1474-4422(24)00495-2]. Lancet Neurol. 2024;23(12):1205-1213. doi:10.1016/S1474-4422(24)00425-3 PMID: 39577921

Timeline to symptomatic Alzheimer's disease in people with Down syndrome as assessed by amyloid-PET and tau-PET: a longitudinal cohort study

通过淀粉样蛋白-PET和tau-PET评估唐氏综合症患者症状性阿尔茨海默病的时间表: 一项纵向队列研究

Adults with Down syndrome are at risk for Alzheimer's disease. Natural history cohort studies have characterised the progression of Alzheimer's disease biomarkers in people with Down syndrome, with a focus on amyloid β-PET and tau-PET. In this study, we aimed to leverage these well characterised imaging biomarkers in a large cohort of individuals with Down syndrome, to examine the timeline to symptomatic Alzheimer's disease based on estimated years since the detection on PET of amyloid β-positivity, referred to here as amyloid age, and in relation to tau burden as assessed by PET. There is a short timeline to initial cognitive decline and dementia from onset of amyloid β positivity and tau deposition in people with Down syndrome. This newly established timeline based on amyloid age (or equivalent centiloid values) is important for clinical practice and informing the design of Alzheimer's disease clinical trials, and it avoids the limitations of timelines based on chronological age.

患有唐氏综合症的成年人有患阿尔茨海默氏病的风险。自然史队列研究已表征了唐氏综合症患者中阿尔茨海默氏病生物标志物的进展，重点是淀粉样蛋白 β-PET和tau-PET。在这项研究中，我们的目标是利用这些充分表征的成像生物标志物在一大群患有唐氏综合症的个体中，根据自PET检测淀粉样蛋白 β 阳性以来的估计年数来检查症状性阿尔茨海默氏病的时间表，这里称为淀粉样蛋白年龄，并与PET评估的tau负荷有关。唐氏综合症患者从淀粉样蛋白 β 阳性和tau沉积开始到最初的认知能力下降和痴呆的时间很短。这种基于淀粉样蛋白年龄 (或等效的centiloid值) 的新建立的时间线对于临床实践和告知阿尔茨海默氏病临床试验的设计是重要的，并且它避免了基于实足年龄的时间线的限制。

REF: Schworer EK, Zammit MD, Wang J, et al. Timeline to symptomatic Alzheimer's disease in people with Down syndrome as assessed by amyloid-PET and tau-PET: a longitudinal cohort study. Lancet Neurol. 2024;23(12):1214-1224. doi:10.1016/S1474-4422(24)00426-5 PMID: 39577922

Sensitivity and specificity of a seed amplification assay for diagnosis of multiple system atrophy: a multicentre cohort study

种子扩增法诊断多系统萎缩的敏感性和特异性: 一项多中心队列研究

The pathological hallmarks of multiple system atrophy and Parkinson's disease are, respectively, misfolded-α-synuclein-laden glial cytoplasmic inclusions and Lewy bodies. CSF-soluble misfolded α-synuclein aggregates (seeds) are readily detected in people with Parkinson's disease by α-synuclein seed amplification assay (synSAA), but identification of seeds associated with multiple system atrophy for diagnostic purposes has proven elusive. We aimed to assess whether a novel synSAA could reliably distinguish seeds from Lewy bodies and glial cytoplasmic inclusions. The novel synSAA produced amplification patterns that enabled the identification of underlying α-synuclein pathology, showing two levels of fluorescence that corresponded with different pathological hallmarks of synucleinopathy. The synSAA might be useful for early diagnosis of synucleinopathies in clinical trials, and potentially for clinical use, but additional formal validation work is needed.

多系统萎缩和帕金森氏病的病理标志分别是错误折叠的 α-突触核蛋白负载的胶质细胞质内含物和路易体。通过 α-突触核蛋白种子扩增测定 (synSAA) 在患有帕金森氏病的人中容易检测到CSF可溶性错误折叠的 α-突触核蛋白聚集体 (种子)，但是为了诊断目的鉴定与多系统萎缩相关的种子已被证明是难以捉摸的。我们旨在评估一种新的synSAA是否可以可靠地将种子与路易体和神经胶质细胞质内含物区分开。新的synSAA产生了扩增模式，能够识别潜在的 α-突触核蛋白病理，显示出两种水平的荧光，与突触核蛋白病的不同病理标志相对应。synSAA可能对临床试验中的突触核蛋白病的早期诊断有用，并且可能用于临床使用，但是需要额外的正式验证工作。

REF: Ma Y, Farris CM, Weber S, et al. Sensitivity and specificity of a seed amplification assay for diagnosis of multiple system atrophy: a multicentre cohort study. Lancet Neurol. 2024;23(12):1225-1237. doi:10.1016/S1474-4422(24)00395-8 PMID: 39577923

Post-mortem neuropathology of idiopathic rapid eye movement sleep behaviour disorder: a case series

特发性快速眼动睡眠行为障碍的死后神经病理学: 病例系列

Idiopathic rapid eye movement (REM) sleep behaviour disorder (IRBD) is thought to be an early stage of α-synuclein-related neurodegenerative diseases. Nevertheless, the definitive identification of its biological substrate can be determined only by post-mortem neuropathology. We aimed to describe the post-mortem neuropathology of individuals with IRBD who developed or did not develop a neurodegenerative disease before death. Although limited by a relatively small sample size, our observations provide strong neuropathological evidence that IRBD is an early stage of α-synuclein-related neurodegenerative disease. Concomitant pathologies are frequent and their role remains to be clarified: some might have contributed to the development of dementia, but some might be age-related changes. Our findings could inform the design of clinical trials of compounds that target specific pathological proteins (eg, α-synuclein and amyloid β) in people with IRBD.

特发性快速眼动 (REM) 睡眠行为障碍 (IRBD) 被认为是 α-突触核蛋白相关神经退行性疾病的早期阶段。尽管如此，其生物底物的最终鉴定只能通过死后神经病理学来确定。我们旨在描述IRBD患者在死亡前发生或未发生神经退行性疾病的死后神经病理学。尽管受到相对较小的样本量的限制，但我们的观察结果提供了强有力的神经病理学证据，表明IRBD是 α-突触核蛋白相关神经退行性疾病的早期阶段。伴随的病理是常见的，它们的作用仍有待澄清: 有些可能导致痴呆的发展，但有些可能与年龄相关的变化。我们的发现可以为针对IRBD患者中特定病理蛋白 (例如 α-突触核蛋白和淀粉样蛋白 β) 的化合物的临床试验设计提供信息。

REF: Mayà G, Iranzo A, Gaig C, et al. Post-mortem neuropathology of idiopathic rapid eye movement sleep behaviour disorder: a case series. Lancet Neurol. 2024;23(12):1238-1251. doi:10.1016/S1474-4422(24)00402-2 PMID: 39577924

Multiple system atrophy: advances in pathophysiology, diagnosis, and treatment

多系统萎缩: 病理生理学、诊断和治疗进展

Multiple system atrophy is an adult-onset, sporadic, and progressive neurodegenerative disease. People with this disorder report a wide range of motor and non-motor symptoms. Overlap in the clinical presentation of multiple system atrophy with other movement disorders (eg, Parkinson's disease and progressive supranuclear palsy) is a concern for accurate and timely diagnosis. Over the past 5 years, progress has been made in understanding key pathophysiological events in multiple system atrophy, including the seeding of α-synuclein inclusions and the detection of disease-specific α-synuclein strains. Diagnostic criteria were revised in 2022 with the intention to improve the accuracy of a diagnosis of multiple system atrophy, particularly for early disease stages. Early signals of efficacy in clinical trials have indicated the potential for disease-modifying therapies for multiple system atrophy, although no trial has yet provided unequivocal evidence of neuroprotection in this rare disease. The advances in pathophysiology could play a part in biomarker discovery for early diagnosis as well as in the development of disease-modifying therapies.

多系统萎缩是一种成人发病、散发性和进行性神经退行性疾病。患有这种疾病的人报告了广泛的运动和非运动症状。多系统萎缩的临床表现与其他运动障碍 (例如，帕金森病和进行性核上性麻痹) 重叠是准确和及时诊断的问题。在过去的5年中，在了解多系统萎缩的关键病理生理事件方面取得了进展，包括接种 α-突触核蛋白内含物和检测疾病特异性 α-突触核蛋白菌株。2022年修订了诊断标准，旨在提高多系统萎缩诊断的准确性，特别是对于早期疾病阶段。临床试验中疗效的早期信号表明，多系统萎缩的疾病改善疗法具有潜力，尽管尚无试验提供明确的证据证明这种罕见疾病的神经保护作用。病理生理学的进展可能在早期诊断的生物标志物发现以及疾病改善疗法的发展中发挥作用。

REF: Krismer F, Fanciulli A, Meissner WG, Coon EA, Wenning GK. Multiple system atrophy: advances in pathophysiology, diagnosis, and treatment. Lancet Neurol. 2024;23(12):1252-1266. doi:10.1016/S1474-4422(24)00396-X PMID: 39577925