Revue neurologique最新文献_第6页

Chronic meningoencephalitis due to enterovirus A71 complicating rituximab therapy 肠病毒A71引起的慢性脑膜脑炎合并利妥昔单抗治疗。

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique

Pub Date : 2025-12-01 DOI: 10.1016/j.neurol.2025.09.003

A. David , M. Claudé , G. Martin de Frémont , G. Trédez , C. Henry

Background

Rituximab and other anti-CD20 therapies are increasingly used in the treatment of autoimmune and hematologic disorders. These treatments are associated with persistent immune impairment, potentially leading to severe infections. We describe a resolutive case of proven chronic enterovirus A71 (EV A71) meningoencephalitis complicating rituximab maintenance therapy for non-Hodgkin lymphoma.

Methods

This article combines an original case report and a literature review of cases of enteroviral meningoencephalitis complicating rituximab treatment.

Results

A 38-year-old man was treated with rituximab and chemotherapy for a mantle cell lymphoma. During maintenance treatment with rituximab, he developed a “hand-foot-mouth disease”, and one month later severe neurological deterioration including quadriparesis and major neurocognitive disorder leading to a diagnosis of chronic enteroviral meningoencephalitis. A treatment associating monthly intravenous immunoglobulins (IVIg) and fluoxetine was initiated two months after neurological symptoms onset, resulting in dramatic clinical improvement within six months. A brief literature review shows that a treatment with high-dose IVIg often results in clinical improvement. Fluoxetine was added in recent reports based on in vitro evidence of anti-viral activity against enteroviruses.

Discussion

Enteroviral infection should be evoked in patients treated with rituximab presenting with an encephalitic symptomatology, and restoring humoral immunity with high-dose IVIg might improve their condition.

背景：利妥昔单抗和其他抗cd20疗法越来越多地用于自身免疫性疾病和血液系统疾病的治疗。这些治疗与持续的免疫损伤有关，可能导致严重的感染。我们描述了一个确诊的慢性肠病毒A71 （EV A71）脑膜脑炎合并利妥昔单抗维持治疗非霍奇金淋巴瘤的决定性病例。方法：本文结合一例原始病例报告和文献复习肠病毒性脑膜脑炎合并利妥昔单抗治疗的病例。结果：一名38岁的男性接受了利妥昔单抗和化疗治疗套细胞淋巴瘤。在利妥昔单抗维持治疗期间，他出现了“手足口病”，一个月后，严重的神经系统恶化，包括四肢瘫和严重的神经认知障碍，导致诊断为慢性肠病毒脑膜脑炎。在神经系统症状出现两个月后开始每月静脉注射免疫球蛋白（IVIg）和氟西汀治疗，6个月内临床显著改善。一篇简短的文献综述显示，高剂量IVIg治疗通常会导致临床改善。根据对肠道病毒的体外抗病毒活性证据，在最近的报告中添加了氟西汀。讨论：在接受利妥昔单抗治疗的患者出现脑病症状时应引起肠病毒感染，使用大剂量IVIg恢复体液免疫可能改善其病情。

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引用次数: 0

Late-onset epilepsy as a prodromal symptom 迟发性癫痫作为前驱症状

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique

Pub Date : 2025-11-01 DOI: 10.1016/j.neurol.2025.07.007

S. Dupont

Late-onset epilepsy (LOE) of unknown etiology accounts for 15–30% of all LOE cases. A critical question is whether these unexplained seizures represent a prodromal manifestation of an underlying neurological disorder — most notably, stroke or Alzheimer's disease (AD). Growing evidence suggests that seizures may be an early sign of subclinical cerebrovascular disease, serving as a warning signal for future stroke, or an early symptom of a neurodegenerative disorder, particularly AD, reflecting initial pathological changes such as amyloid-β and tau deposition. An alternative hypothesis proposes that shared risk factors — especially cardiovascular ones — underlie all three conditions: LOE, stroke, and AD. As a result, it is recommended that patients with LOE of unknown etiology undergo comprehensive cardiovascular evaluation and receive appropriate management of any identified risk factors. However, it remains unclear whether this approach is sufficient to prevent future strokes. Cognitive assessment is also essential in these patients. In this context, prodromal seizures may provide an opportunity to identify individuals suitable for early, targeted interventions aimed at slowing neurodegeneration.

病因不明的晚发性癫痫（LOE）占所有LOE病例的15-30%。一个关键的问题是，这些无法解释的癫痫发作是否代表一种潜在神经系统疾病的前驱表现——最明显的是中风或阿尔茨海默病（AD）。越来越多的证据表明，癫痫发作可能是亚临床脑血管疾病的早期征兆，是未来中风的警告信号，或者是神经退行性疾病的早期症状，特别是阿尔茨海默病，反映了淀粉样蛋白β和tau沉积等初始病理变化。另一种假说认为，共同的风险因素——尤其是心血管风险因素——构成了这三种疾病的基础：爱情、中风和阿尔茨海默病。因此，建议病因不明的LOE患者进行全面的心血管评估，并对任何确定的危险因素进行适当的管理。然而，目前尚不清楚这种方法是否足以预防未来的中风。在这些患者中，认知评估也是必不可少的。在这种情况下，前驱癫痫发作可能提供了一个机会，以确定个人适合早期，有针对性的干预，旨在减缓神经变性。

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引用次数: 0

In vivo molecular imaging of brain tissue pathology in presymptomatic multiple sclerosis 症状前多发性硬化症脑组织病理的体内分子成像

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique

Pub Date : 2025-11-01 DOI: 10.1016/j.neurol.2025.07.015

V.A.G. Ricigliano , B. Stankoff

The presence of focal lesions suggestive of multiple sclerosis (MS) seen with magnetic resonance imaging (MRI) in asymptomatic individuals defines the radiologically isolated syndrome (RIS). Pathologically, tissue changes in RIS subjects recapitulate, although being less extensive and pronounced, those observed in definite MS, with an amount of innate immune cell activation, myelin loss, gliosis, metabolic modifications, and structural damage affecting the neuro-axonal compartment. Conventional MRI, however, is not able to capture these biological abnormalities at the cellular and molecular level. Positron emission tomography (PET) with specific radiolabeled compounds could fill this gap, identifying in vivo and with higher granularity the processes underling the abnormal MRI signals. This review presents data obtained with PET in RIS individuals and discusses the potential application of this technique in exploring the different pathophysiologic changes going on in the RIS brain, with technical considerations on radiotracers already tested in MS or newly developed. By breaking up the study of complex tissular changes into single biological phenomena, the use of PET in RIS could encourage early interventions to selectively target each one of them, with potential consequences on the clinical conversion to MS.

无症状个体在磁共振成像（MRI）中出现提示多发性硬化症（MS）的局灶性病变定义为放射隔离综合征（RIS）。病理上，RIS患者的组织变化虽然不像明确的MS患者那样广泛和明显，但仍有一定数量的先天免疫细胞激活、髓磷脂丢失、胶质增生、代谢改变和影响神经轴突室的结构损伤。然而，传统的MRI不能在细胞和分子水平上捕捉这些生物学异常。具有特定放射性标记化合物的正电子发射断层扫描（PET）可以填补这一空白，在体内以更高的粒度识别异常MRI信号下的过程。这篇综述介绍了用PET在RIS个体中获得的数据，并讨论了该技术在探索RIS大脑中发生的不同病理生理变化方面的潜在应用，以及已经在MS中测试或新开发的放射性示踪剂的技术考虑。通过将复杂组织变化的研究分解为单一的生物学现象，PET在RIS中的应用可以鼓励早期干预，选择性地针对其中的每一种，从而对临床向MS的转化产生潜在的影响。

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引用次数: 0

Presymptomatic multiple sclerosis: Insights from the Radiologically Isolated Syndrome 症状前多发性硬化症：来自影像学孤立综合征的见解。

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique

Pub Date : 2025-11-01 Epub Date: 2025-08-07 DOI: 10.1016/j.neurol.2025.06.013

C. Lebrun-Frenay , M. Cohen , D.T. Okuda

Radiologically isolated syndrome (RIS) represents the initial phase of multiple sclerosis (MS) and is identified incidentally in asymptomatic individuals who display typical brain or spinal cord lesions indicative of autoimmune inflammatory demyelination. The 2023 RIS criteria enhance diagnostic precision against imaging mimics by requiring one T2-weighted hyperintense lesion in two of four specified locations (periventricular, juxtacortical/cortical, infratentorial, spinal cord) alongside at least two of the following: a spinal cord lesion, CSF-restricted oligoclonal bands (OCB), or a new T2/gadolinium-enhancing lesion on MRI at any point, defining dissemination in time (DIT). After confirming the diagnosis, established risk factors for transition to clinical MS need to be assessed. Key factors include a younger age, male sex, the presence of infratentorial, spinal cord, or gadolinium-enhancing lesions, and CSF-restricted OCBs or increased kappa-free light chains. Two randomized trials showed the efficacy of two oral disease-modifying therapies in delaying the first clinical event in RIS. However, as some individuals remain asymptomatic, it's crucial to identify suitable candidates to balance treatment benefits with potential risks. Reviewing each RIS case with an MS expert team is advisable for better care and monitoring. The updated 2024 McDonald criteria classify RIS patients with additional features, such as positive CSF and susceptibility MRI biomarkers, as having preclinical MS.

放射分离综合征（RIS）代表多发性硬化症（MS）的初始阶段，偶然发现于表现出典型的自身免疫性炎症性脱髓鞘的脑或脊髓病变的无症状个体。2023年RIS标准通过要求在四个指定位置（脑室周围、皮质旁/皮质、幕下、脊髓）中的两个位置出现一个T2加权高信号病变，以及以下至少两个：脊髓病变、csf限制性低克隆带（OCB），或在任何点MRI上出现新的T2/钆增强病变，从而提高了对成像模拟的诊断精度（DIT）。确诊后，需要评估已确定的向临床多发性硬化症过渡的危险因素。关键因素包括年龄较小、男性、幕下、脊髓或钆增强病变的存在、csf受限的ocb或无kappa轻链增加。两项随机试验显示两种口腔疾病改善疗法在延迟RIS患者首次临床事件方面的疗效。然而，由于有些人仍然无症状，因此确定合适的候选人以平衡治疗益处与潜在风险至关重要。建议与多发性硬化症专家小组一起审查每个RIS病例，以获得更好的护理和监测。更新的2024年McDonald标准将RIS患者分类为具有其他特征的患者，如CSF阳性和易感性MRI生物标志物，为临床前MS。

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引用次数: 0

Discussing with our patient a presymptomatic adult-onset neurological disease 与患者讨论成人发病前的神经系统疾病。

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique

Pub Date : 2025-11-01 Epub Date: 2025-08-08 DOI: 10.1016/j.neurol.2025.04.010

C. Lebrun-Frenay

引用次数: 0

Presymptomatic detection of spinal muscular atrophy: Ongoing revolution for a devastating disorder 脊髓性肌萎缩症的症状前检测：一种破坏性疾病的持续革命

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique

Pub Date : 2025-11-01 DOI: 10.1016/j.neurol.2025.08.005

V. Laugel

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterized by progressive degeneration of motoneurons, which used to lead in many cases to severe motor impairment and early death without treatment. In recent years, three disease-modifying treatments have dramatically changed the patient outcome, especially when initiated in the presymptomatic phase. This review examines the scientific rationale, practical implications as well as ethical, economic and political considerations of presymptomatic detection of SMA in the era of transformative therapies. The need for early detection and early treatment of SMA has prompted the implementation of newborn screening programs. All clinical trials and real-life surveys have consistently demonstrated the clear benefits of this strategy for patients. This DNA-based newborn screening method followed by gene-related treatments has inaugurated a new paradigm and has challenged the organization of healthcare systems. This strategy has raised ethical questions about management of uncertainties, which should be overcome by long-term follow-up and transparent information given to the parents. Cost-effectiveness studies have shown that the SMA newborn screening strategy is always dominant over post-symptomatic treatment. Despite the compelling evidence accumulating in favor of newborn screening for SMA, the implementation of systematic routine programs has faced political hurdles in many cases and is not yet effective even in all EU countries. The experience of SMA newborn screening will probably be helpful for upcoming genomic newborn screenings.

脊髓性肌萎缩症（SMA）是一种常染色体隐性遗传疾病，以运动神经元进行性变性为特征，在许多病例中，如果不进行治疗，会导致严重的运动障碍和早期死亡。近年来，三种改善疾病的治疗方法极大地改变了患者的预后，特别是在症状前阶段开始治疗时。本文综述了在变革疗法时代，SMA症状前检测的科学原理、实际意义以及伦理、经济和政治考虑。早期发现和早期治疗SMA的需要促使了新生儿筛查项目的实施。所有临床试验和现实生活调查都一致证明了这种策略对患者的明显益处。这种以dna为基础的新生儿筛查方法，随后是基因相关治疗，开创了一个新的范例，并挑战了卫生保健系统的组织。这一策略引发了关于管理不确定性的伦理问题，应该通过长期跟踪和向父母提供透明的信息来克服这些问题。成本效益研究表明，SMA新生儿筛查策略总是优于症状后治疗。尽管越来越多的令人信服的证据支持对新生儿进行SMA筛查，但在许多情况下，系统常规项目的实施面临政治障碍，即使在所有欧盟国家也尚未有效。SMA新生儿筛查的经验可能会对即将到来的新生儿基因组筛查有所帮助。

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引用次数: 0

Diagnostic & therapeutic challenges of presymptomatic hereditary transthyretin amyloidosis 症状前遗传性甲状腺转蛋白淀粉样变的诊断和治疗挑战

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique

Pub Date : 2025-11-01 DOI: 10.1016/j.neurol.2025.06.016

A. Echaniz-Laguna , V. Algalarrondo

Hereditary transthyretin amyloidosis (ATTRv) is a rare, lethal, autosomal dominant adult-onset genetic disorder provoked by mutations in the TTR gene. Until recently, therapeutic options were limited to liver transplantation and TTR stabilizers. Antisense oligonucleotides (ASO) and small interfering RNA (siRNA) treatments, now commercially available, have dramatically improved ATTRv neurological outcome, and affected patients’ relatives are increasingly being identified at the presymptomatic stage. Guidelines for monitoring presymptomatic patients have been established by different groups. ATTRv disease onset is defined by a combination of pathologically proven amyloid TTR deposits, symptoms attributed to ATTRv, and clinical changes in comparison with initial assessment. However, several studies have shown that many presymptomatic patients present with subclinical abnormalities before amyloid deposits are observed, blurring the boundary between presymptomatic and symptomatic statuses. Future challenges include identifying biomarkers for better delineating the transition between presymptomatic and symptomatic, e.g., neurofilament light chain (NfL), and considering prophylactic treatment to prevent the onset of the disease.

遗传性甲状腺转蛋白淀粉样变性（ATTRv）是一种罕见的、致命的、常染色体显性的成人发病遗传疾病，由TTR基因突变引起。直到最近，治疗选择仅限于肝移植和TTR稳定剂。反义寡核苷酸（ASO）和小干扰RNA （siRNA）治疗现已商业化，显著改善了ATTRv的神经预后，并且越来越多的患者亲属在症状前阶段被识别出来。不同群体已经建立了监测症状前患者的指南。ATTRv疾病的发病是由病理学证实的淀粉样TTR沉积、ATTRv引起的症状以及与最初评估相比的临床变化共同确定的。然而，一些研究表明，许多症状前患者在观察到淀粉样蛋白沉积之前就已经出现亚临床异常，这模糊了症状前和症状状态之间的界限。未来的挑战包括识别生物标志物，以更好地描述症状前和症状之间的转变，例如神经丝轻链（NfL），并考虑预防性治疗以预防疾病的发生。

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引用次数: 0

Markers of presymptomatic amyotrophic lateral sclerosis: State of the art, practical implications and perspectives 症状前肌萎缩性侧索硬化症的标志物：现状，实际意义和观点

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique

Pub Date : 2025-11-01 DOI: 10.1016/j.neurol.2025.07.008

M.-H. Soriani , H. Blasco , P. Corcia , V. Danel-Brunaud , A. Desmaison , P.-F. Pradat , G. Querin , P. Vourch , N. Guy

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an identified genetic origin in 10–15% of cases, mainly involving C9orf72 and SOD1 mutations. The increasing number of genetically confirmed ALS cases has led to a growing identification of asymptomatic mutation carriers. While riluzole remains the standard treatment, mutation-specific therapies such as tofersen, that was recently approved in SOD1-ALS, are emerging. In this context, the identification of presymptomatic biomarkers is crucial for monitoring genetically at-risk individuals. Plasma neurofilament light chain can increase up to 3.5 years before symptom onset in C9orf72 carriers. Metabolic and neuroimaging alterations together with cognitive or behavioral changes, that are sometimes detectable decades prior to diagnosis, have also been observed. These biomarkers may support early surveillance and intervention strategies. The present review provides an overview of current evidence on presymptomatic biomarkers in ALS mutation carriers and their potential role in genetic counseling, monitoring, and early therapeutic decisions.

肌萎缩性侧索硬化症（ALS）是一种神经退行性疾病，在10-15%的病例中有确定的遗传起源，主要涉及C9orf72和SOD1突变。越来越多的基因证实ALS病例导致越来越多的无症状突变携带者的识别。虽然利鲁唑仍然是标准的治疗方法，但突变特异性治疗如最近被批准用于治疗SOD1-ALS的托佛森正在出现。在这种情况下，识别症状前生物标志物对于监测遗传风险个体至关重要。C9orf72携带者的血浆神经丝轻链可在症状出现前3.5年增加。代谢和神经影像学的改变以及认知或行为的改变，有时在诊断前几十年就可以检测到。这些生物标志物可能支持早期监测和干预策略。本综述概述了ALS突变携带者症状前生物标志物的现有证据及其在遗传咨询、监测和早期治疗决策中的潜在作用。

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引用次数: 0

Lessons learned from 30 years of presymptomatic testing in Huntington Disease 从30年的亨廷顿病症状前检测中得到的经验教训

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique

Pub Date : 2025-11-01 DOI: 10.1016/j.neurol.2025.07.009

L. Pierron , M. Hébert , M. Gargiulo , A. Durr

Presymptomatic testing allows individuals to undergo genetic testing for inherited diseases before symptoms manifest. While valuable in conditions with available preventive strategies, no therapeutic prevention currently exists for Huntington disease, making testing a personal choice rather than a medical recommendation. Available in France since 1992 – following the identification of CAG repeat expansions (> 35) in the huntingtin gene – presymptomatic testing is governed by guidelines emphasizing autonomy, benevolence, informed consent, confidentiality, and equity. Its implementation requires an interdisciplinary approach, including genetic counseling and psychological support, to ensure comprehensive care. One of the many lessons learned is that despite the large availability of presymptomatic testing centers, less than 20% of at-risk individuals choose to be tested, reflecting complex psychological and familial dynamics. In addition, motivations for testing vary widely, more often identified as the desire to know rather than family planning, which explains the even lower opting in for prenatal testing. Psychological support is essential, as an unfavorable result puts individuals in a prolonged liminal state, waiting for disease onset. Favorable results are the happy ending of testing, but can, in some instances, also trigger complex emotional responses, such as survivor's guilt. Involving presymptomatic carriers in research programs has offered important scientific benefits and also a sense of agency and meaning for participants. Our experience with presymptomatic testing in Huntington disease has established a paradigm for predictive genetic medicine, highlighting the importance of interdisciplinary care and ethical considerations. As genomic medicine advances, the core principles of presymptomatic testing remain relevant, ensuring the protection and consent of individuals and their families. These lessons help to disseminate information about the utility of genetic counseling and call for an informed approach to presymptomatic testing in neurogenetics.

症状前检测允许个体在症状出现之前进行遗传疾病的基因检测。虽然在现有预防策略的条件下很有价值，但目前还没有针对亨廷顿病的治疗性预防措施，这使得检测成为一种个人选择，而不是医学建议。自1992年在法国发现亨廷顿基因CAG重复扩增（> 35）以来，症状前检测遵循强调自主、仁慈、知情同意、保密和公平的指导方针。它的实施需要跨学科的方法，包括遗传咨询和心理支持，以确保全面的护理。我们得到的许多教训之一是，尽管有大量的症状前检测中心，但只有不到20%的高危个体选择接受检测，这反映了复杂的心理和家庭动态。此外，进行检测的动机差别很大，通常被认为是渴望了解而不是计划生育，这就解释了选择产前检测的人更少。心理支持是必不可少的，因为不利的结果使个体处于长时间的阈限状态，等待疾病发作。有利的结果是测试的圆满结局，但在某些情况下，也会引发复杂的情绪反应，比如幸存者的内疚感。在研究项目中涉及症状前携带者提供了重要的科学效益，也为参与者提供了一种能动性和意义感。我们在亨廷顿病症状前检测方面的经验为预测性遗传医学建立了一个范例，强调了跨学科治疗和伦理考虑的重要性。随着基因组医学的进步，症状前检测的核心原则仍然适用，确保个人及其家属得到保护和同意。这些经验教训有助于传播有关遗传咨询的效用的信息，并呼吁在神经遗传学中采取一种知情的方法进行症状前检测。

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引用次数: 0

The challenging concept of preclinical Alzheimer's disease 临床前阿尔茨海默病的挑战性概念

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique

Pub Date : 2025-11-01 DOI: 10.1016/j.neurol.2025.07.016

D. Wallon , A. Garnier-Crussard

Alzheimer's disease (AD) is increasingly recognized as a decades-long process that begins before any first cognitive symptoms. Neuropathology and in vivo biomarker studies have revealed a silent preclinical phase. However, its precise definition and boundaries remain debated. Elucidating the biological events and temporal sequence that characterize this stage is essential, while researchers try to identify the optimal window to prevent or postpone cognitive decline. At the same time, “preclinical AD” raises unresolved challenges in diagnosis, prognosis, therapeutic intervention and ethics. This narrative review synthesizes the current evidence, from clinical characterization to prevention trials and societal considerations, with an emphasis on original findings for amyloid, tau and neurodegeneration biomarkers. We critically contrast the two principal research frameworks that structure the field and examine how each shapes patient classification and trial design. By integrating these lines of evidence, we explore persistent gaps in prognostic modeling and in the clinical efficacy of disease-modifying strategies. The review aims to provide a concise but comprehensive overview of the preclinical concept for clinicians and researchers developing the next generation of preventive interventions for AD.

阿尔茨海默病（AD）越来越被认为是一个长达数十年的过程，在任何最初的认知症状之前就开始了。神经病理学和体内生物标志物研究揭示了沉默的临床前阶段。然而，它的精确定义和边界仍然存在争议。阐明这一阶段的生物学事件和时间序列是至关重要的，同时研究人员试图确定预防或延缓认知衰退的最佳窗口。同时，“临床前阿尔茨海默病”在诊断、预后、治疗干预和伦理等方面提出了尚未解决的挑战。这篇叙述性综述综合了目前的证据，从临床特征到预防试验和社会考虑，重点是淀粉样蛋白、tau和神经变性生物标志物的原始发现。我们批判性地对比了构建该领域的两个主要研究框架，并检查了每个框架如何影响患者分类和试验设计。通过整合这些证据，我们探索了预后模型和疾病改善策略临床疗效方面的持续差距。该综述旨在为临床医生和研究人员开发下一代AD预防干预措施提供一个简明而全面的临床前概念概述。

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引用次数: 0