Azathioprine for the treatment of early Parkinson's disease (AZA-PD): a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial

硫唑嘌呤治疗早期帕金森病（AZA - PD）：一项随机、双盲、安慰剂对照、概念验证性 2 期试验

The immune system is implicated in Parkinson's disease aetiology and prognosis. Although there are effective symptomatic treatments for Parkinson's disease, there are currently no therapies that slow down disease progression. We aimed to investigate the clinical efficacy of the broadly acting peripheral immunosuppressant drug azathioprine for patients with early Parkinson's disease. Azathioprine was well-tolerated in this population; however, the primary outcome was not met. Exploratory analyses suggested effects of azathioprine on peripheral and central immune biomarkers and on motor symptoms. Potential clinical effects could be greater in females than males, warranting further exploration.

免疫系统与帕金森病的病因和预后相关。尽管帕金森病有有效的对症治疗方法，但目前尚无能够减缓疾病进展的疗法。我们旨在研究广泛作用的外周免疫抑制剂硫唑嘌呤对早期帕金森病患者的临床疗效。硫唑嘌呤在该人群中耐受性良好；然而，未达到主要结局。探索性分析表明，硫唑嘌呤对外周和中枢免疫生物标志物以及运动症状有影响。女性患者的潜在临床效果可能比男性更显著，值得进一步探索。

REF: Greenland JC, Dresser K, Cutting E, et al. Azathioprine for the treatment of early Parkinson's disease (AZA-PD): a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial. Lancet Neurol. 2026;25(1):39-49. doi:10.1016/S1474-4422(25)00386-2 PMID: 41389828

Seizure-related biomarkers of sudden unexpected death in epilepsy (SUDEP) in drug-resistant focal epilepsy (REPO2MSE): a prospective, multicentre case–control study

药物难治性局灶性癫痫患者癫痫猝死（SUDEP）的癫痫发作相关生物标志物研究（REPO2MSE）：一项前瞻性、多中心病例对照研究

Novel biomarkers of the risk of sudden unexpected death in epilepsy (SUDEP) are needed to better inform people with epilepsy of their individual risk and identify those at a high risk. The aim of this study was to identify such biomarkers, particularly with the exploration of seizures characteristics that have not been previously investigated, including peri-ictal peripheral oxygen saturation (SpO2) and site of seizure onset. Extratemporal epilepsies involving the perisylvian region or frontal lobe appear to be associated with an increased risk of SUDEP. This finding warrants confirmation in larger cohorts and underscores the need to improve the diagnosis and surgical management of extratemporal epilepsies, which might contribute to improved SUDEP risk stratification and prevention.

需要有新的癫痫患者意外猝死（SUDEP）风险生物标志物，以便更好地让癫痫患者了解自身的个体风险并识别出高危患者。本研究旨在确定此类生物标志物，尤其要探索此前尚未研究过的癫痫发作特征，包括发作期外周血氧饱和度（SpO₂）和癫痫发作起始部位。涉及外侧裂周围区域或额叶的颞外癫痫似乎与SUDEP风险增加有关。这一发现有待在更大的队列中进行验证，并且强调了有必要改进颞外癫痫的诊断和手术治疗，这可能有助于改善SUDEP风险分层和预防。

REF: Ryvlin P, Huot M, Valton L, et al. Seizure-related biomarkers of sudden unexpected death in epilepsy (SUDEP) in drug-resistant focal epilepsy (REPO2MSE): a prospective, multicentre case-control study. Lancet Neurol. 2026;25(1):50-60. doi:10.1016/S1474-4422(25)00379-5 PMID: 41285145

Endovascular thrombectomy for acute stroke: evolving eligibility criteria and adjunct therapies

急性脑卒中的血管内血栓切除术：不断演变的适应证标准和辅助治疗方法

Endovascular thrombectomy is the standard treatment for ischaemic stroke, a leading cause of disability worldwide. Randomised trials in the past decade have expanded eligibility criteria to include broader patient populations, such as those with large ischaemic core stroke. However, many patients still have poor outcomes despite high rates of macrovascular reperfusion, underscoring the need for strategies that go beyond restoring large-vessel flow. Intra-arterial thrombolysis and cytoprotective agents are under investigation for their potential to reduce secondary complications during and after endovascular thrombectomy. These strategies target key mechanisms such as microvascular obstruction, excitotoxicity, oxidative stress, and inflammation. Their effectiveness depends on aligning the mechanism of action with the patient's underlying pathophysiology. Despite years of promising results limited by constrained clinical translation in cytoprotective trials, recent trials have provided hope and insights, helping to define crucial factors for translational success. Incorporating these lessons into refined inclusion criteria and future studies has the potential to transform our approach to caring for patients at the greatest risk of poor clinical outcomes, including severe disability or death.

血管内血栓切除术是缺血性卒中的标准治疗方法，缺血性卒中是全球致残的主要原因。过去十年的随机试验已将符合治疗条件的患者范围扩大到更多人群，比如大面积缺血核心梗死的患者。然而，尽管大血管再通率很高，但许多患者的预后仍然不佳，这凸显了需要采取超越恢复大血管血流的治疗策略。动脉内溶栓和细胞保护剂正在研究中，以评估其在血管内血栓切除术中及术后减少继发性并发症的潜力。这些策略针对微血管阻塞、兴奋性毒性、氧化应激和炎症等关键机制。其有效性取决于作用机制是否与患者的潜在病理生理状况相匹配。尽管多年来细胞保护剂试验取得了有前景的结果，但临床转化受限。不过，近期试验带来了希望并提供了见解，有助于明确转化成功的关键因素。将这些经验纳入优化的纳入标准和未来研究中，有可能改变我们对临床预后不良（包括严重残疾或死亡）高风险患者的治疗方式。

REF: Glavan M, Liu J, Sampaio Silva G, et al. Endovascular thrombectomy for acute stroke: evolving eligibility criteria and adjunct therapies. Lancet Neurol. 2026;25(1):61-76. doi:10.1016/S1474-4422(25)00356-4 PMID: 41389830

Emerging technologies and strategies in epilepsy surgery: toward personalised medicine

癫痫手术中的新兴技术与策略：迈向个性化医疗

Epilepsy surgery, the treatment of choice for drug-resistant focal epilepsy, is evolving rapidly. This progress is driven by a growing interest in the network theory of epilepsy, advances in data-driven models, and a focus on personalised treatment approaches. As a result, treatment options have expanded to include minimally invasive procedures, neurostimulation devices, and network-based interventions. Predicting surgical outcomes-such as seizure freedom and neuropsychological effects-remains challenging but is improving through advances in computational technology and molecular research, paving the way for more precise surgery. Despite these advancements, disparities in access to treatments persist, particularly in resource-scarce settings, highlighting the need for systemic solutions to improve access. Emerging research into genetic and multi-omic markers might assist in tailoring treatments and improving the prediction of outcomes. Future directions include integrating minimally invasive techniques, refining neuromodulation strategies, and leveraging molecular and computational tools to optimise patient care. Multidisciplinary collaboration will be essential to overcome challenges, reduce disparities, and advance surgical outcomes for patients with drug-resistant epilepsy worldwide.

癫痫手术作为药物难治性局灶性癫痫的首选治疗方法，正迅速发展。这一进展得益于人们对癫痫网络理论兴趣的日益浓厚、数据驱动模型的进步，以及对个性化治疗方法的关注。因此，治疗选择已扩展到包括微创手术、神经刺激设备和基于网络的干预措施。预测手术结果（如癫痫发作缓解和神经心理影响）仍然具有挑战性，但随着计算技术和分子研究的进展，情况正在改善，这为更精准的手术铺平了道路。尽管取得了这些进展，但在获得治疗方面的差距仍然存在，特别是在资源匮乏的地区，这凸显了需要系统性解决方案来改善治疗可及性。对基因和多组学标志物的新兴研究可能有助于量身定制治疗方案并提高结果预测的准确性。未来的发展方向包括整合微创技术、完善神经调节策略，以及利用分子和计算工具来优化患者护理。多学科合作对于克服挑战、减少差距以及改善全球药物难治性癫痫患者的手术结果至关重要。

REF: Yardi R, Englot DJ, Wu C, et al. Emerging technologies and strategies in epilepsy surgery: toward personalised medicine. Lancet Neurol. 2026;25(1):77-89. doi:10.1016/S1474-4422(25)00380-1 PMID: 41389832

The role of lifestyle interventions in symptom management and disease modification in Parkinson's disease

生活方式干预在帕金森病症状管理和疾病改善中的作用

Emerging evidence indicates that sustainable lifestyle changes-such as increasing physical activity, adopting healthy dietary patterns, and managing stress-can provide symptomatic benefits and potentially slow neurodegeneration in Parkinson's disease. Combining these interventions could produce synergistic effects, addressing multiple aspects of the pathophysiology. Despite the challenges of long-term adherence, innovative approaches such as digital tools and personalised strategies can support sustained lifestyle modifications. Tailoring interventions to individual needs and cultural contexts is crucial, especially in diverse socioeconomic settings. Future research should focus on large-scale, long-term studies to better understand the disease-modifying potential of lifestyle interventions and explore the biological mechanisms underlying their benefits. Overall, integrating lifestyle modifications into routine care offers a promising, accessible avenue to improve quality of life and potentially alter the progression of Parkinson's disease.

越来越多的证据表明，可持续的生活方式改变——如增加体育活动、采用健康的饮食模式和管理压力——可以改善帕金森病的症状，并有可能减缓神经退行性病变。将这些干预措施相结合可能会产生协同效应，从多个方面改善病理生理状况。尽管长期坚持这些改变存在挑战，但数字工具和个性化策略等创新方法可以支持人们持续做出生活方式的调整。根据个人需求和文化背景量身定制干预措施至关重要，在社会经济背景多样的环境中尤为如此。未来的研究应侧重于开展大规模、长期的研究，以更好地了解生活方式干预对改变疾病进程的潜力，并探索其有益作用背后的生物学机制。总体而言，将生活方式的调整纳入常规护理，为改善帕金森病患者的生活质量、并有可能改变疾病的进展提供了一条有望实现且切实可行的途径。

REF: Trinh J, de Vries NM, Chan P, Dekker MCJ, Helmich RC, Bloem BR. The role of lifestyle interventions in symptom management and disease modification in Parkinson's disease. Lancet Neurol. 2026;25(1):90-102. doi:10.1016/S1474-4422(25)00305-9 PMID: 41109323