Annals of Neurology
本篇文献由机器智能翻译
Current State of Evidence for Neuroimaging Paradigms in Management of Acute Ischemic Stroke
急性缺血性卒中管理中神经影像学范例的证据现状
Stroke is the chief differential diagnosis in patient presenting to the emergency room with abrupt onset focal neurological deficits. Neuroimaging, including non-contrast computed tomography (CT), magnetic resonance imaging (MRI), vascular and perfusion imaging, is a cornerstone in the diagnosis and treatment decision-making. This review examines the current state of evidence behind the different imaging paradigms for acute ischemic stroke diagnosis and treatment, including current recommendations from the guidelines. Non-contrast CT brain, or in some centers MRI, can help differentiate ischemic stroke and intracerebral hemorrhage (ICH), a pivotal juncture in stroke diagnosis and treatment algorithm, especially for early window thrombolytics. Advanced imaging such as MRI or perfusion imaging can also assist making a diagnosis of ischemic stroke versus mimics such as migraine, Todd's paresis, or functional disorders. Identification of medium-large vessel occlusions with CT or MR angiography triggers consideration of endovascular thrombectomy (EVT), with additional perfusion imaging help identify salvageable brain tissue in patients who are likely to benefit from reperfusion therapies, particularly in the ≥6 h window. We also review recent advances in neuroimaging and ongoing trials in key therapeutic areas and their imaging selection criteria to inform the readers on potential future transitions into use of neuroimaging for stroke diagnosis and treatment decision making. ANN NEUROL 2024;95:1017–1034
中风是患者因突然发作的局灶性神经功能缺损而出现急诊室的主要鉴别诊断疾病。神经影像学,包括非对比计算机断层扫描 (CT),磁共振成像 (MRI),血管和灌注成像,是诊断和治疗决策的基石。这篇综述研究了急性缺血性卒中诊断和治疗的不同影像学范例背后的证据现状,包括指南的当前建议。非对比CT脑,或在某些中心MRI,可以帮助区分缺血性中风和脑出血 (ICH),这是中风诊断和治疗算法的关键时刻,尤其是对于早期窗溶栓。先进的成像,如MRI或灌注成像,也可以帮助诊断缺血性中风与模拟如偏头痛,托德的面瘫,或功能障碍。通过CT或MR血管造影识别中大血管闭塞,可考虑进行血管内血栓切除术 (EVT),额外的灌注成像有助于识别可能从再灌注治疗中受益的患者可挽救的脑组织,尤其是在 ≥ 6?H窗口。我们还回顾了神经影像学的最新进展和关键治疗领域正在进行的试验及其影像学选择标准,以告知读者将来可能过渡到使用神经影像学进行中风诊断和治疗决策。安·诺伊尔·2024;95:1017-1034
REF: Sarraj A, Pujara DK, Campbell BC. Current State of Evidence for Neuroimaging Paradigms in Management of Acute Ischemic Stroke. Ann Neurol. 2024;95(6):1017-1034. doi:10.1002/ana.26925 PMID: 38606939
Beyond the Final Heartbeat: Neurological Perspectives on Normothermic Regional Perfusion for Organ Donation after Circulatory Death
超越最后的心跳: 循环死亡后器官捐赠的正常体温区域灌注的神经学观点
Normothermic regional perfusion (NRP) has recently been used to augment organ donation after circulatory death (DCD) to improve the quantity and quality of transplantable organs. In DCD-NRP, after withdrawal of life-sustaining therapies and cardiopulmonary arrest, patients are cannulated onto extracorporeal membrane oxygenation to reestablish blood flow to targeted organs including the heart. During this process, aortic arch vessels are ligated to restrict cerebral blood flow. We review ethical challenges including whether the brain is sufficiently reperfused through collateral circulation to allow reemergence of consciousness or pain perception, whether resumption of cardiac activity nullifies the patient's prior death determination, and whether specific authorization for DCD-NRP is required.
最近,常温区域灌注 (NRP) 已用于增加循环死亡 (DCD) 后的器官捐赠,以提高可移植器官的数量和质量。在dcd-nrp中,在撤回生命维持疗法和心肺骤停后,将患者插管到体外膜氧合中以重建到包括心脏在内的靶器官的血流。在此过程中,结扎主动脉弓血管以限制脑血流量。我们回顾了伦理挑战,包括大脑是否通过侧支循环充分再灌注以重新出现意识或疼痛感,心脏活动的恢复是否使患者先前的死亡确定无效,以及是否需要dcd-nrp的特定授权。
REF: Kirschen MP, Lewis A, Rubin MA, Varelas PN, Greer DM. Beyond the Final Heartbeat: Neurological Perspectives on Normothermic Regional Perfusion for Organ Donation after Circulatory Death. Ann Neurol. 2024;95(6):1035-1039. doi:10.1002/ana.26926 PMID: 38501716
Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property
伴皮质下梗死和白质脑病的促出血性常染色体显性遗传性脑动脉病伴NOTCH3 p.R75P突变伴低血管NOTCH3聚集特性
Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties.
伴有皮质下梗塞和白质脑病的常染色体显性遗传性脑动脉病的脑出血 (ICH) 和脑微出血 (CMB) 在东亚人群中比在欧洲白人血统的人群中更为常见。我们假设种族差异是由东亚特异性NOTCH3 p.R75P突变解释的。Notch3p.R75P突变与出血表现,轻度颞极病变和不同的突变蛋白结构特性有关。
REF: Ishiyama H, Kim H, Saito S, et al. Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property. Ann Neurol. 2024;95(6):1040-1054. doi:10.1002/ana.26916 PMID: 38520151
Lifetime Stressful Events Associated with Alzheimer's Pathologies, Neuroinflammation and Brain Structure in a Risk Enriched Cohort
风险富集队列中与阿尔茨海默氏病,神经炎症和脑结构相关的终生压力事件
Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD. We did not find evidence supporting the association of total SLEs with AD, neuroinflammation, and atrophy pathways. Instead, the associations appear to be contingent on events occurring during early and midlife, sex and history of psychiatric disease.
随着已知的压力对大脑结构和炎症过程的影响,越来越多的证据表明慢性压力在阿尔茨海默氏病 (AD) 的发病机理中起作用。我们调查了认知未受损 (CU) 个体中AD风险增加的累积应激性生活事件 (SLEs) 与AD病理,神经炎症和灰质 (GM) 体积的关系。我们没有发现证据支持总SLEs与AD,神经炎症和萎缩途径的关联。相反,这些关联似乎取决于早期和中年发生的事件,性别和精神疾病史。
REF: Palpatzis E, Akinci M, Aguilar-Dominguez P, et al. Lifetime Stressful Events Associated with Alzheimer's Pathologies, Neuroinflammation and Brain Structure in a Risk Enriched Cohort. Ann Neurol. 2024;95(6):1058-1068. doi:10.1002/ana.26881 PMID: 38466157
Diet, Pace of Biological Aging, and Risk of Dementia in the Framingham Heart Study
Framingham心脏研究中的饮食,生物衰老速度和痴呆风险
People who eat healthier diets are less likely to develop dementia, but the biological mechanism of this protection is not well understood. We tested the hypothesis that healthy diet protects against dementia because it slows the pace of biological aging. Findings suggest that slower pace of aging mediates part of the relationship of healthy diet with reduced dementia risk. Monitoring pace of aging may inform dementia prevention. However, a large fraction of the diet-dementia association remains unexplained and may reflect direct connections between diet and brain aging that do not overlap other organ systems. Investigation of brain-specific mechanisms in well-designed mediation studies is warranted.
饮食健康的人患痴呆症的可能性较小,但这种保护的生物学机制尚不清楚。我们测试了健康饮食可以预防痴呆症的假设,因为它可以减缓生物衰老的速度。研究结果表明,较慢的衰老速度介导了健康饮食与降低痴呆症风险的部分关系。监测衰老的速度可能有助于预防痴呆症。然而,很大一部分饮食与痴呆的关联仍然无法解释,可能反映了饮食与大脑衰老之间的直接联系,而这些联系并不与其他器官系统重叠。在精心设计的调解研究中研究大脑特定的机制是必要的。
REF: Thomas A, Ryan CP, Caspi A, et al. Diet, Pace of Biological Aging, and Risk of Dementia in the Framingham Heart Study. Ann Neurol. 2024;95(6):1069-1079. doi:10.1002/ana.26900 PMID: 38407506
Cognitive Impairment Is Related to Glymphatic System Dysfunction in Pediatric Multiple Sclerosis
小儿多发性硬化症的认知障碍与淋巴系统功能障碍有关
The aim of this study was to investigate whether, compared to pediatric healthy controls (HCs), the glymphatic system is impaired in pediatric multiple sclerosis (MS) patients according to their cognitive status, and to assess its association with clinical disability and MRI measures of brain structural damage. Glymphatic system dysfunction occurs in pediatric MS, is associated with brain focal lesions, irreversible tissue loss accumulation and cognitive impairment.
这项研究的目的是调查与儿科健康对照 (HCs) 相比,儿科多发性硬化症 (MS) 患者的淋巴系统是否根据其认知状况受损,并评估其与临床残疾和MRI措施的关系脑结构损伤。淋巴系统功能障碍发生在小儿MS中,与脑局灶性病变,不可逆转的组织损失积累和认知障碍有关。
REF: Margoni M, Pagani E, Meani A, et al. Cognitive Impairment Is Related to Glymphatic System Dysfunction in Pediatric Multiple Sclerosis. Ann Neurol. 2024;95(6):1080-1092. doi:10.1002/ana.26911 PMID: 38481063
Real-World Healthcare Cost Savings and Reduced Relapse Rate with Off-Label Rituximab versus Disease-Modifying Treatments Approved for Relapsing–Remitting Multiple Sclerosis: A Nationwide Cost-Effectiveness Study
与批准用于复发缓解型多发性硬化症的疾病改善治疗相比,超说明书利妥昔单抗节省了真实世界的医疗成本并降低了复发率: 一项全国性的成本效益研究
Although off-label use of rituximab is a common alternative to disease-modifying therapies (DMTs) approved for multiple sclerosis (MS) in several countries, the impact of this on treatment cost-effectiveness is not well known. The cost-effectiveness of rituximab dominated the MS-approved alternatives. Off-label, low-dose rituximab should be considered for persons with MS and could reduce barriers to treatment, especially in resource-limited settings.
尽管超说明书使用利妥昔单抗是多个国家批准用于多发性硬化症 (MS) 的疾病改善疗法 (dmt) 的常见替代方案,但其对治疗成本效益的影响尚不清楚。利妥昔单抗的成本效益主导了MS批准的替代方案。超说明书,MS患者应考虑使用低剂量利妥昔单抗,这可以减少治疗障碍,尤其是在资源有限的情况下。
REF: Alping P, Neovius M, Piehl F, Frisell T. Real-World Healthcare Cost Savings and Reduced Relapse Rate with Off-Label Rituximab versus Disease-Modifying Treatments Approved for Relapsing-Remitting Multiple Sclerosis: A Nationwide Cost-Effectiveness Study. Ann Neurol. 2024;95(6):1099-1111. doi:10.1002/ana.26914 PMID: 38529711
HLA Associations of Intrathecal IgG Production against Specific Viruses in Multiple Sclerosis
多发性硬化症中针对特定病毒的鞘内IgG产生的HLA关联
Specific human leucocyte antigen (HLA) alleles are not only associated with higher risk to develop multiple sclerosis (MS) and other autoimmune diseases, but also with the severity of various viral and bacterial infections. Here, we analyzed the most specific biomarker for MS, that is, the polyspecific intrathecal IgG antibody production against measles, rubella, and varicella zoster virus (MRZ reaction), for possible HLA associations in MS. HLA-DRB1*15:01, the strongest genetic risk factor for MS, and female sex, 1 of the most prominent demographic risk factors for developing MS, predispose in MS/CIS patients for a positive MRZ reaction, the most specific CSF biomarker for MS.
特定的人类白细胞抗原 (HLA) 等位基因不仅与发展多发性硬化症 (MS) 和其他自身免疫性疾病的高风险相关,而且还与各种病毒和细菌感染的严重程度相关。在这里,我们分析了MS最特异性的生物标志物,即针对麻疹,风疹和水痘带状疱疹病毒 (MRZ反应) 的多特异性鞘内IgG抗体产生,以了解MS中可能的HLA关联。HLA-DRB1 * 15:01,MS最强的遗传风险因素,和女性,1发展MS的最突出的人口统计学危险因素之一,在MS/CIS患者中倾向于阳性MRZ反应,这是MS的最特异性CSF生物标志物。
REF: Neidhart S, Vlad B, Hilty M, et al. HLA Associations of Intrathecal IgG Production against Specific Viruses in Multiple Sclerosis. Ann Neurol. 2024;95(6):1112-1126. doi:10.1002/ana.26921 PMID: 38551149
Is High-Frequency Activity at Seizure Onset Inhibitory? A Stereoelectroencephalographic Study of Motor Cortex Seizures
癫痫发作时的高频活动是抑制性的吗?运动皮质癫痫发作的立体脑电图研究
In the era of stereoelectroencephalography (SEEG), many studies have been devoted to understanding the role of interictal high-frequency oscillations. High-frequency activity (HFA) at seizure onset has been identified as a marker of epileptogenic zone. We address the physiological significance of ictal HFAs and their relation to clinical semiology. This study supports the hypothesis of an inhibitory effect of ictal HFAs. The frequency range in the gamma band was associated with the direction of the clinical output effect. Changes from inhibitory to excitatory effect occurred when discharge frequency dropped to low gamma or beta.
在立体脑电图 (SEEG) 时代,许多研究致力于理解发作间高频振荡的作用。癫痫发作时的高频活动 (HFA) 已被确定为癫痫发生区的标志物。我们讨论了发作性hfa的生理意义及其与临床符号学的关系。这项研究支持了ictal hfa抑制作用的假设。伽玛波段的频率范围与临床输出效果的方向有关。当放电频率降至低 γ 或 β 时,发生了从抑制作用到兴奋作用的变化。
REF: Shaker H, Li J, Kobayashi M, et al. Is High-Frequency Activity at Seizure Onset Inhibitory? A Stereoelectroencephalographic Study of Motor Cortex Seizures. Ann Neurol. 2024;95(6):1127-1137. doi:10.1002/ana.26883 PMID: 38481022
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