Effects of blood pressure lowering in relation to time in acute intracerebral haemorrhage: a pooled analysis of the four INTERACT trials

急性脑出血降血压时机的影响：四项急性脑出血积极降压治疗（INTERACT）试验的汇总分析

Uncertainty remains about the effects of intensive blood pressure (BP) lowering in acute intracerebral haemorrhage, particularly the impact of treatment timing. This study aimed to assess the safety and effectiveness of early intensive BP-lowering treatment and its dependence on timing in patients with intracerebral haemorrhage. Intensive BP-lowering initiated within several hours of intracerebral haemorrhage onset was safe and improved functional recovery, without a clear effect on haematoma growth. The greatest benefits for both outcomes occurred when treatment was commenced within 3 h of symptom onset. These findings underscore the importance of early intervention and inform the design of future trials targeting patients at highest risk of haematoma expansion.

急性脑出血患者强化降压治疗的效果，尤其是治疗时机的影响，仍存在不确定性。本研究旨在评估脑出血患者早期强化降压治疗的安全性和有效性，以及其对治疗时机的依赖性。脑出血发作后数小时内开始强化降压治疗是安全的，且能改善功能恢复，对血肿扩大无明显影响。症状发作后3小时内开始治疗，在上述两方面的获益最大。这些发现强调了早期干预的重要性，并为未来针对血肿扩大高风险患者的试验设计提供了参考。

REF: Wang X, Ren X, Li Q, et al. Effects of blood pressure lowering in relation to time in acute intracerebral haemorrhage: a pooled analysis of the four INTERACT trials. Lancet Neurol. 2025;24(7):571-579. doi:10.1016/S1474-4422(25)00160-7 PMID: 40541207

Diagnostic and prognostic value of α-synuclein seed amplification assay kinetic measures in Parkinson's disease: a longitudinal cohort study

α-突触核蛋白种子扩增分析动力学指标在帕金森病中的诊断和预后价值：一项纵向队列研究

α-synuclein seed amplification assay (SAA) positivity has been proposed as a diagnostic biomarker for Parkinson's disease. However, studies of the prognostic value of this biomarker have been limited to small, single-centre studies over short follow-up periods. We aimed to assess the diagnostic and prognostic value of quantitative CSF α-synuclein SAA kinetic measures in Parkinson's disease. Assessing α-synuclein SAA kinetic measures might aid in the diagnostic differentiation of Parkinson's disease from progressive supranuclear palsy with Lewy body co-pathology. Furthermore, faster seeding kinetics are found in GBA1-Parkinson's disease and predict cognitive decline in Parkinson's disease independently of Alzheimer's disease co-pathology.

α-突触核蛋白种子扩增分析（SAA）阳性已被提议作为帕金森病的诊断生物标志物。然而，关于该生物标志物预后价值的研究仅限于短期随访的小型单中心研究。我们旨在评估脑脊液定量α-突触核蛋白SAA动力学指标在帕金森病中的诊断和预后价值。评估α-突触核蛋白SAA动力学指标可能有助于在诊断上区分帕金森病与伴有路易小体共病的进行性核上性麻痹。此外，在GBA1相关帕金森病中发现种子形成动力学更快，并且该指标可独立于阿尔茨海默病共病预测帕金森病患者的认知衰退。

REF: Orrú CD, Vaughan DP, Vijiaratnam N, et al. Diagnostic and prognostic value of α-synuclein seed amplification assay kinetic measures in Parkinson's disease: a longitudinal cohort study. Lancet Neurol. 2025;24(7):580-590. doi:10.1016/S1474-4422(25)00157-7 PMID: 40541208

Prediction of amyloid and tau brain deposition and cognitive decline in people with Down syndrome using plasma biomarkers: a longitudinal cohort study

利用血浆生物标志物预测唐氏综合征患者的脑淀粉样蛋白和tau蛋白沉积及认知衰退：一项纵向队列研究

Plasma biomarkers associated with Alzheimer's disease could improve prognostic assessment for people with Down syndrome in both clinical practice and research settings. We aimed to identify the plasma biomarkers that most accurately predict longitudinal changes in Alzheimer's disease-related pathology and cognitive functioning in individuals with Down syndrome. Baseline and longitudinal plasma p-tau217 were associated with subsequent decline in global cognition, progression to dementia, and increased tau burden, whereas baseline p-tau217 and GFAP were associated with Aβ accumulation. These findings suggest that plasma p-tau217 and GFAP might be valuable for prognostic assessment of Alzheimer's disease in people with Down syndrome in both clinical and research contexts. The results further support evaluation of these biomarkers for monitoring disease progression in clinical trials of Down syndrome-related Alzheimer's disease.

与阿尔茨海默病相关的血浆生物标志物可在临床实践和研究环境中改善唐氏综合征患者的预后评估。我们旨在确定能够最准确预测唐氏综合征患者与阿尔茨海默病相关的病理和认知功能纵向变化的血浆生物标志物。基线和纵向血浆磷酸化tau蛋白217（p - tau217）与随后的整体认知能力下降、痴呆进展以及tau蛋白负荷增加相关，而基线p - tau217和胶质纤维酸性蛋白（GFAP）与β - 淀粉样蛋白（Aβ）积聚相关。这些发现表明，血浆p - tau217和GFAP在临床和研究背景下对唐氏综合征患者的阿尔茨海默病预后评估可能具有重要价值。研究结果进一步支持在唐氏综合征相关阿尔茨海默病的临床试验中评估这些生物标志物以监测疾病进展。

REF: Janelidze S, Collij LE, Mattsson-Carlgren N, et al. Prediction of amyloid and tau brain deposition and cognitive decline in people with Down syndrome using plasma biomarkers: a longitudinal cohort study. Lancet Neurol. 2025;24(7):591-600. doi:10.1016/S1474-4422(25)00158-9 PMID: 40541209

Management of reproductive risks in people with epilepsy

癫痫患者生殖风险的管理

Epilepsy is a common neurological condition worldwide, presenting unique management challenges for those affected during reproductive age. The effectiveness of contraceptives can be modified by antiseizure medication treatments and pregnancy can alter the pharmacokinetics of antiseizure medications. Furthermore, although treatment with some antiseizure medications convey lifelong risks to offspring, inadequately controlled epilepsy can lead to injury or, in rare cases, death of the mother. In this complex set of circumstances, safe and effective antiseizure medication treatment, evidence-based decision making regarding contraceptive selections, and clear counselling and risk minimisation are imperative. Although risk-benefit decision making has become standard clinical practice for the management of women with epilepsy of childbearing age, reproductive treatment considerations could also be relevant for men. Most young adults with epilepsy live in low-income and middle-income countries, where access to contraceptives, antiseizure medications with adequate safety profiles, and reproductive care and counselling can be scarce. Strategies to optimise care for people with epilepsy in all stages of their reproductive journey must be tailored for resource-limited settings to improve parent-child health worldwide.

癫痫是全球常见的神经系统疾病，给育龄患者的管理带来了独特挑战。抗癫痫药物治疗可能会影响避孕药的效果，而怀孕则可能改变抗癫痫药物的药代动力学。此外，尽管某些抗癫痫药物治疗会给后代带来终生风险，但癫痫控制不佳可能导致母亲受伤，极少数情况下甚至会导致死亡。在这一复杂情况下，安全有效的抗癫痫药物治疗、基于循证的避孕药选择决策、清晰的咨询和风险最小化措施至关重要。虽然风险 - 获益决策已成为育龄癫痫女性管理的标准临床实践，但生殖治疗方面的考虑对男性也可能有意义。大多数年轻癫痫患者生活在低收入和中等收入国家，在这些国家，获得避孕药、具有足够安全性的抗癫痫药物以及生殖保健和咨询的机会可能十分有限。为优化癫痫患者在整个生殖过程各阶段的护理而制定的策略，必须根据资源有限的环境进行调整，以改善全球范围内的亲子健康状况。

REF: Bjørk MH, Cukiert C, Nucera B, Bromley RL. Management of reproductive risks in people with epilepsy. Lancet Neurol. 2025;24(7):601-613. doi:10.1016/S1474-4422(25)00130-9 PMID: 40541210

Friedreich's ataxia—a rare multisystem disease

弗里德赖希共济失调——一种罕见的多系统疾病

Friedreich's ataxia is a rare autosomal recessive neurodegenerative disease. Most patients have a homozygous GAA repeat expansion in the FXN gene, resulting in a deficiency of the mitochondrial protein frataxin. Disease onset occurs typically in adolescence but can vary widely, ranging from early childhood to late adulthood. Friedreich's ataxia is increasingly recognised as a multisystem disorder, affecting not only the nervous system, but also the heart and musculoskeletal system, and metabolism. Common extraneural manifestations include cardiomyopathy, which is the most common cause of mortality, and also scoliosis and diabetes. Despite research advances, the phenotypical heterogeneity of patients with Friedrich's ataxia remains inadequately explained by current knowledge of the underlying genetics. The approval of omaveloxolone by the US Food and Drug Administration and the European Medicines Agency has been a pharmacological milestone; however, further research addressing complex interorgan interactions is crucial for a better understanding of the multisystem nature of Friedreich's ataxia and the development of targeted treatment approaches.

弗里德赖希共济失调是一种罕见的常染色体隐性神经退行性疾病。大多数患者的FXN基因存在纯合GAA重复扩增，导致线粒体蛋白frataxin缺乏。疾病通常在青春期发病，但发病时间差异很大，从幼儿期到成年晚期都有可能。弗里德赖希共济失调越来越被认为是一种多系统疾病，不仅影响神经系统，还会影响心脏、肌肉骨骼系统和代谢。常见的神经外表现包括心肌病（这是最常见的死亡原因），还有脊柱侧凸和糖尿病。尽管研究取得了进展，但目前对潜在遗传学的认识仍不足以解释弗里德赖希共济失调患者的表型异质性。美国食品药品监督管理局和欧洲药品管理局批准奥马韦洛索隆是一个药理学上的里程碑；然而，进一步开展针对复杂器官间相互作用的研究，对于更好地理解弗里德赖希共济失调的多系统特性以及开发有针对性的治疗方法至关重要。

REF: Reetz K, Lischewski SA, Dogan I, et al. Friedreich's ataxia-a rare multisystem disease. Lancet Neurol. 2025;24(7):614-624. doi:10.1016/S1474-4422(25)00175-9 PMID: 40541211