Extended CT angiography versus standard CT angiography for the detection of cardioaortic thrombus in patients with ischaemic stroke and transient ischaemic attack (DAYLIGHT): a prospective, randomised, open-label, blinded end-point trial

延长 CT 血管造影与标准 CT 血管造影用于检测缺血性卒中和短暂性脑缺血发作患者心脏和主动脉血栓（DAYLIGHT）：一项前瞻性、随机、开放标签、盲法终点试验

Cardioembolic sources often remain undetected after standard diagnostic stroke workup, contributing to high rates of recurrence. We aimed to assess whether a head-to-neck CT angiography extended at least 6 cm below the carina (extended CT angiography) can increase the detection of cardioaortic thrombi compared with standard-of-care CT angiography (standard CT angiography) in patients with ischaemic stroke or transient ischaemic attack. Performing extended CT angiography during acute code strokes is feasible and results in increased cardioaortic thrombi detection without causing delays in CT angiography completion. Future studies should assess whether extended CT angiography can reduce recurrent stroke risk by prompting early anticoagulation after thrombus detection.

在标准的卒中诊断检查后，心源性栓塞源往往仍未被发现，这导致了较高的复发率。我们旨在评估与标准治疗的 CT 血管造影（标准 CT 血管造影）相比，延伸至隆突以下至少 6 厘米的头颈部 CT 血管造影（延伸 CT 血管造影）是否能提高缺血性卒中或短暂性脑缺血发作患者心主动脉血栓的检出率。在急性卒中急救时进行延伸 CT 血管造影是可行的，且能提高心主动脉血栓的检出率，同时不会导致 CT 血管造影检查完成时间的延迟。未来的研究应评估延伸 CT 血管造影能否通过在检测到血栓后及时启动抗凝治疗来降低卒中复发风险。

REF: Sposato LA, Ayan D, Ahmed M, et al. Extended CT angiography versus standard CT angiography for the detection of cardioaortic thrombus in patients with ischaemic stroke and transient ischaemic attack (DAYLIGHT): a prospective, randomised, open-label, blinded end-point trial. Lancet Neurol. 2025;24(6):489-499. doi:10.1016/S1474-4422(25)00111-5 PMID: 40409313

Safety and efficacy of trehalose in amyotrophic lateral sclerosis (HEALEY ALS Platform Trial): an adaptive, phase 2/3, double-blind, randomised, placebo-controlled trial

海藻糖治疗肌萎缩侧索硬化的安全性和有效性（HEALEY 肌萎缩侧索硬化平台试验）：一项适应性 2/3 期双盲随机安慰剂对照试验

Trehalose is a disaccharide that activates autophagy pathways in animal models of neurodegenerative diseases, with the potential to catalyse clearance of toxic, misfolded proteins in motor neurons and slow disease progression in amyotrophic lateral sclerosis (ALS). We aimed to evaluate the safety and efficacy of trehalose in individuals with ALS. Trehalose was well tolerated but there was no evidence to suggest a difference in ALS disease progression compared with placebo in this study. No statistical benefit was seen in secondary clinical or biomarker measures, suggesting that trehalose at this dosage is unlikely to be efficacious for treatment of ALS.

海藻糖是一种二糖，在神经退行性疾病的动物模型中可激活自噬途径，有可能促进运动神经元中有毒的错误折叠蛋白的清除，并减缓肌萎缩侧索硬化症（ALS）的疾病进展。我们旨在评估海藻糖对肌萎缩侧索硬化症患者的安全性和有效性。本研究中，海藻糖耐受性良好，但没有证据表明与安慰剂相比，其能改变肌萎缩侧索硬化症的疾病进展情况。在次要临床指标或生物标志物指标方面也未观察到统计学上的益处，这表明该剂量的海藻糖不太可能对肌萎缩侧索硬化症的治疗有效。

REF: HEALEY ALS Platform Trial; HEALEY ALS Platform Trial Study Group. Safety and efficacy of trehalose in amyotrophic lateral sclerosis (HEALEY ALS Platform Trial): an adaptive, phase 2/3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2025;24(6):500-511. doi:10.1016/S1474-4422(25)00173-5 PMID: 40409314

A new characterisation of acute traumatic brain injury: the NIH-NINDS TBI Classification and Nomenclature Initiative

急性创伤性脑损伤的新特征描述：美国国立卫生研究院 - 国立神经疾病和中风研究所创伤性脑损伤分类与命名倡议

The clinical severity of traumatic brain injury (TBI) is commonly classified according to the Glasgow Coma Scale (GCS) sum score as mild (13-15), moderate (9-12), or severe (3-8). A new approach is needed for characterising TBI more accurately. In 2022, the US National Institutes of Health-National Institute of Neurological Disorders and Stroke launched an international initiative to address this need, with a focus on the acute phase of injury. Six working groups of TBI experts, implementation scientists, people with lived experience, and federal partners were established, involving 94 participants from 14 countries. The proposed new framework for the characterisation of acute TBI incorporates four pillars: a clinical pillar (full GCS and pupillary reactivity); a biomarker pillar (blood-based measures); an imaging pillar (pathoanatomical measures); and a modifier pillar (features influencing clinical presentation and outcome; CBI-M). The CBI-M framework provides a multidimensional characterisation of TBI to inform individualised clinical management and to improve scientific rigor. Research priorities include validation of the CBI-M framework, evaluation of its applicability beyond the acute phase of TBI, and strategies for clinical implementation.

创伤性脑损伤（TBI）的临床严重程度通常根据格拉斯哥昏迷量表（GCS）总分进行分类，分为轻度（13 - 15分）、中度（9 - 12分）或重度（3 - 8分）。需要一种新方法来更准确地表征创伤性脑损伤。2022年，美国国立卫生研究院 - 国家神经疾病和中风研究所发起了一项国际倡议以满足这一需求，重点关注损伤的急性期。成立了由创伤性脑损伤专家、实施科学家、有亲身经历者和联邦合作伙伴组成的六个工作组，来自14个国家的94名参与者参与其中。提议的急性创伤性脑损伤表征新框架包含四大支柱：临床支柱（完整的GCS和瞳孔反应性）；生物标志物支柱（基于血液的检测指标）；影像学支柱（病理解剖学检测指标）；以及修饰因素支柱（影响临床表现和预后的特征；CBI - M）。CBI - M框架对创伤性脑损伤进行多维度表征，为个体化临床管理提供依据并提高科学严谨性。研究重点包括验证CBI - M框架、评估其在创伤性脑损伤急性期之后的适用性，以及临床实施策略。

REF: Manley GT, Dams-O'Connor K, Alosco ML, et al. A new characterisation of acute traumatic brain injury: the NIH-NINDS TBI Classification and Nomenclature Initiative. Lancet Neurol. 2025;24(6):512-523. doi:10.1016/S1474-4422(25)00154-1 PMID: 40409315

Protective genetic variants against Alzheimer's disease

对抗阿尔茨海默病的保护性基因变异

Genetic studies can offer powerful insights for the development of disease-modifying therapies for Alzheimer's disease. Protective genetic variants that delay the onset of cognitive impairment have been found in people with sporadic Alzheimer's disease and in carriers of mutations that usually cause autosomal-dominant Alzheimer's disease in mid-life. The study of families who carry autosomal dominant mutations provides a unique opportunity to uncover genetic modifiers of disease progression, including rare variants in genes such as APOE and RELN. Understanding how these variants confer protection can help identify the biological pathways that contribute to cognitive resilience, such as the heparan-sulphate proteoglycan-APOE receptor pathway, the TREM-2-driven signalling pathways in the microglia, and phagocytosis. Therapies able to replicate the beneficial effects of these natural defences could provide novel strategies for slowing or preventing the progression of Alzheimer's disease.

基因研究可为开发改变阿尔茨海默病病程的疗法提供有力见解。在散发性阿尔茨海默病患者以及通常会在中年引发常染色体显性遗传性阿尔茨海默病的突变携带者中，已发现能延缓认知障碍发作的保护性基因变异。对携带常染色体显性突变的家族进行研究，为揭示疾病进展的基因修饰因子提供了独特契机，这些修饰因子包括载脂蛋白E（APOE）和Reelin（RELN）等基因中的罕见变异。了解这些变异如何提供保护作用，有助于确定促成认知恢复力的生物途径，如硫酸乙酰肝素蛋白聚糖 - APOE受体途径、小胶质细胞中由触发受体表达蛋白2（TREM - 2）驱动的信号通路以及吞噬作用。能够复制这些天然防御有益效果的疗法，可为减缓或阻止阿尔茨海默病的进展提供新策略。

REF: Marino C, Malotaux V, Giudicessi A, et al. Protective genetic variants against Alzheimer's disease. Lancet Neurol. 2025;24(6):524-534. doi:10.1016/S1474-4422(25)00116-4 PMID: 40409316

CSF transport at the brain–meningeal border: effects on neurological health and disease

脑 - 脑膜边界处的脑脊液运输：对神经健康与疾病的影响

The existence of specialised structures that allow a continuous exchange of CSF between different anatomical compartments at the brain-meningeal border is challenging conventional notions around molecular transport within the brain. Experimental findings highlight the conduits and cellular structures controlling the transport of CSF and immune cells between the brain parenchyma (via the glymphatic system), the subarachnoid space (enclosed by the meningeal pia and arachnoid layers), and the outmost meningeal dural layer and calvaria (via the so-called arachnoid cuff exit points). Studies in both rodent models and humans show new mechanisms of brain glymphatic molecular transport, meningeal lymphatic vascular drainage, and immune surveillance at the brain-draining skull bone marrow and cervical lymph nodes. Pathological alterations at the brain-meningeal border have been implicated in disorders of diverse causes, from traumatic brain injury to Alzheimer's disease.

在脑 - 脑膜边界存在允许不同解剖腔室之间持续进行脑脊液（CSF）交换的特殊结构，这对围绕大脑内分子运输的传统观念提出了挑战。实验结果突显了控制脑脊液和免疫细胞在脑实质（通过类淋巴系统）、蛛网膜下腔（由软脑膜和蛛网膜层包裹）、最外层的硬脑膜层和颅骨（通过所谓的蛛网膜袖套出口点）之间运输的管道和细胞结构。对啮齿动物模型和人类的研究揭示了脑类淋巴分子运输、脑膜淋巴管引流以及脑引流颅骨骨髓和颈淋巴结免疫监视的新机制。脑 - 脑膜边界的病理改变与多种病因的疾病有关，从创伤性脑损伤到阿尔茨海默病。

REF: Pinho-Correia LM, McCullough SJC, Ghanizada H, Nedergaard M, Rustenhoven J, Da Mesquita S. CSF transport at the brain-meningeal border: effects on neurological health and disease. Lancet Neurol. 2025;24(6):535-547. doi:10.1016/S1474-4422(25)00115-2 PMID: 40409317