Chemotherapy-Related Cognitive Impairment and Changes in Neural Network Dynamics: A Systematic Review

化疗相关认知障碍与神经网络动力学变化的系统综述

This systematic review aims to synthesize the current literature on the association between chemotherapy (CTX) and chemotherapy-related cognitive impairment (CRCI) with functional and structural brain alterations in patients with noncentral nervous system cancers. While there is evidence suggesting CTX affects brain connectivity and neural network dynamics that can lead to cognitive difficulties, the findings are inconsistent. More robust and standardized research is needed to conclusively determine the extent of these effects and to develop targeted interventions for mitigating potential cognitive impairments in patients undergoing systemic treatment.

这项系统综述旨在综合有关非中枢神经系统癌症患者化疗 (CTX) 和化疗相关认知障碍 (CRCI) 与功能性和结构性脑改变之间关系的最新文献。虽然有证据表明CTX会影响大脑连接和神经网络动力学，从而导致认知困难，但研究结果并不一致。需要更强有力和标准化的研究来最终确定这些影响的程度，并开发有针对性的干预措施，以减轻接受系统治疗的患者的潜在认知障碍。

REF: Leskinen S, Alsalek S, Galvez R, et al. Chemotherapy-Related Cognitive Impairment and Changes in Neural Network Dynamics: A Systematic Review. Neurology. 2025;104(2):e210130. doi:10.1212/WNL.0000000000210130 PMID: 39804577

Effect of Triheptanoin on Caudate Atrophy and Motor Scores in Patients With Early-Stage Huntington Disease: A Phase II Study

三庚酸甘油酯对早期亨廷顿病患者尾状核萎缩和运动评分的影响: 一项II期研究

Brain energy deficiency occurs at the early stage of Huntington disease (HD). Triheptanoin, a drug that targets the Krebs cycle, can restore a normal brain energetic profile in patients with HD. In this study, we aimed at assessing its efficacy on clinical and neuroimaging structural measures in HD. There was no effect of triheptanoin on caudate atrophy over 6 months. Compared with the external placebo group, triheptanoin was associated with motor stability and decreased caudate atrophy in patients treated for 12 months, but the post hoc nature of these findings is a major limitation.

脑能量缺乏发生在亨廷顿病 (HD) 的早期阶段。三庚酸甘油酯是一种针对克雷布斯循环的药物，可以使HD患者恢复正常的大脑活力。在这项研究中，我们旨在评估其在HD中的临床和神经影像学结构测量中的功效。三庚酸甘油酯在6个月内对尾状萎缩没有影响。与外部安慰剂组相比，三庚酸甘油酯与治疗12个月的患者的运动稳定性和尾状核萎缩减少有关，但这些发现的事后性质是一个主要限制。

REF: Mochel F, Méneret A, Adanyeguh IM, et al. Effect of Triheptanoin on Caudate Atrophy and Motor Scores in Patients With Early-Stage Huntington Disease: A Phase II Study. Neurology. 2025;104(2):e210194. doi:10.1212/WNL.0000000000210194 PMID: 39804569

Association of Sleep Spindle Rate With Memory Consolidation in Children With Rolandic Epilepsy

罗兰癫痫患儿睡眠纺锤率与记忆巩固的关系

Rolandic epilepsy (RE), the most common childhood focal epilepsy syndrome, is characterized by a transient period of sleep-activated epileptiform activity in the centrotemporal regions and variable cognitive deficits. Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in RE and related sleep-activated epileptic encephalopathies. To further evaluate the association between this electrographic biomarker and cognitive dysfunction in this common disease, we investigate whether children with RE have deficient sleep-dependent memory consolidation and whether impaired memory consolidation is associated with reduced sleep spindles in the centrotemporal regions. Children with RE have impaired sleep-dependent memory consolidation during the active period of disease that correlates with a deficit in the sleep spindle rate. This finding identifies a noninvasive biomarker to aid diagnosis and a potential etiologic mechanism to guide therapeutic discovery of cognitive dysfunction in RE and related sleep-activated epilepsy syndromes.

罗兰性癫痫 (RE) 是最常见的儿童局灶性癫痫综合征，其特征是在中央颞部区域出现短暂的睡眠激活的癫痫样活动和可变的认知缺陷。睡眠纺锤波是睡眠期间突出的丘脑皮质脑振荡，其与动物模型和健康对照中的睡眠依赖性记忆巩固有机械联系。在RE和相关的睡眠激活的癫痫性脑病中，睡眠纺锤降低。为了进一步评估这种电图生物标志物与这种常见疾病的认知功能障碍之间的关系，我们调查了RE儿童是否有睡眠依赖性记忆巩固不足，以及记忆巩固受损是否与中央颞区睡眠纺锤降低有关。患有RE的儿童在疾病活动期的睡眠依赖性记忆巩固受损，这与睡眠纺锤体速率的不足有关。这一发现确定了一种非侵入性生物标志物，以帮助诊断和潜在的病因机制，以指导RE和相关的睡眠激活癫痫综合征中认知功能障碍的治疗发现。

REF: Kwon H, Chinappen DM, Kinard EA, et al. Association of Sleep Spindle Rate With Memory Consolidation in Children With Rolandic Epilepsy. Neurology. 2025;104(2):e210232. doi:10.1212/WNL.0000000000210232 PMID: 39804468 PMCID: PMC11684947

Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study

静脉注射Onasemnogene Abeparvovec治疗小儿脊髓性肌萎缩症的安全性和有效性: 3b期SMART研究

Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.5-21 kg. Onasemnogene abeparvovec safety profile was similar across weight groups in this heterogenous participant population. Frequency and duration of asymptomatic aminotransferase elevations and thrombocytopenia are notable findings. Most participants demonstrated maintenance or improvement of motor function, suggesting clinical benefit for patients with SMA weighing up to 21 kg.

对于体重 <8.5千克的脊髓性肌萎缩症 (SMA) 患者，已经证明了静脉注射onasemnogene abeparvovec的安全性和有效性。SMART是第一个评估体重8.5-21千克的参与者的onasemnogene abeparvovec的临床试验。在这个异质参与者人群中，不同体重组的Onasemnogene abeparvovec安全性相似。无症状转氨酶升高和血小板减少症的频率和持续时间是值得注意的发现。大多数参与者表现出运动功能的维持或改善，这表明体重高达21千克的SMA患者具有临床益处。

REF: McMillan HJ, Baranello G, Farrar MA, et al. Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study. Neurology. 2025;104(2):e210268. doi:10.1212/WNL.0000000000210268 PMID: 39804575 PMCID: PMC11694182

Pearls & Oy-sters: Increased Visibility of Focal Cortical Dysplasia in Cerebral MRI During the First Year of Life

珍珠和牡蛎: 生命第一年大脑MRI中局灶性皮质发育不良的可见度增加

Early detection of focal cortical dysplasia (FCD) using brain MRI in young children presenting with drug-resistant epilepsy may facilitate prompt surgical treatment, resulting in better control of seizures and decreased associated cognitive difficulties. Characteristics of FCD described in the literature are predominantly based on MRI findings in a fully myelinated brain; therefore, changes occurring during early brain maturation are not well known. In this case report, we describe distinct MRI features of a FCD visualized best before completion of myelination of the cortex and subcortical white matter. Specifically, this lesion exhibited increased visibility because of better delineation of the borders of the pathological area involved in the malformation compared with imaging obtained after completion of myelination. Although the pathophysiology of these imaging features necessitates further investigation, one hypothesis is that excessive neuronal input in young epileptic patients could trigger premature myelination of overstimulated fibers underlying the cortical epileptogenic focus. The aim of this case report was to raise awareness that seizures might induce local changes in brain myelination, which can be detected by MRI during the first year of life. Early identification of FCD may prompt surgical treatment in selected patients with drug-resistant epilepsy.

使用脑部MRI对患有耐药性癫痫的幼儿进行局灶性皮质发育不良 (FCD) 的早期检测可能有助于迅速进行手术治疗，从而更好地控制癫痫发作并减少相关的认知困难。文献中描述的FCD的特征主要基于完全有髓鞘的大脑中的MRI发现; 因此，在早期大脑成熟期间发生的变化尚不清楚。在本病例报告中，我们描述了在皮质和皮质下白质髓鞘形成完成之前FCD最佳可视化的独特MRI特征。具体而言，与髓鞘形成完成后获得的成像相比，由于更好地描绘了畸形所涉及的病理区域的边界，因此该病变的可见度提高。尽管这些影像学特征的病理生理学需要进一步研究，但一种假设是，年轻癫痫患者过多的神经元输入可能会触发皮质癫痫灶下方过度刺激的纤维过早髓鞘化。本病例报告的目的是提高人们对癫痫发作可能引起脑髓鞘形成局部变化的认识，这可以在生命的第一年通过MRI检测到。早期发现FCD可能会提示某些耐药性癫痫患者进行手术治疗。

REF: Visvaratnam H, Korff CM, Seeck M, Fitsiori A. Pearls & Oy-sters: Increased Visibility of Focal Cortical Dysplasia in Cerebral MRI During the First Year of Life. Neurology. 2025;104(2):e210128. doi:10.1212/WNL.0000000000210128 PMID: 39729603 PMCID: PMC11675710

Clinical Reasoning: A 35-Year-Old Woman With Personality Change and Gait Impairment

临床推理: 一名35岁女性，人格改变和步态障碍

A 35-year-old woman presented with a progressive 3-year history of personality changes and gait impairment. Neurologic examination revealed bilateral optic atrophy, spastic paraparesis, and impaired vibratory sensation in all limbs, and neuropsychological evaluation identified a frontotemporal cognitive impairment. In this article, we review the differential diagnosis for a young woman with chronic frontotemporal dysfunction, optic atrophy, and dorsolateral myelopathy in a stepwise multidisciplinary approach. Critical information obtained from the medical history led to a final diagnosis.

一名35岁的女性出现了3年的人格改变和步态障碍史。神经系统检查显示双侧视神经萎缩，痉挛性截瘫和所有肢体的振动感觉受损，神经心理学评估确定了额颞认知障碍。在本文中，我们以逐步的多学科方法回顾了患有慢性额颞功能障碍，视神经萎缩和背外侧脊髓病的年轻女性的鉴别诊断疾病。从病史中获得的关键信息导致了最终诊断。

REF: Bernardes C, Lemos JM, Santo GC. Clinical Reasoning: A 35-Year-Old Woman With Personality Change and Gait Impairment. Neurology. 2025;104(2):e210252. doi:10.1212/WNL.0000000000210252 PMID: 39729612

Clinical Reasoning: Clinical Manifestations and Diagnostic Challenges in a 16-Year-Old With Early-Onset Ataxia

临床推理: 16岁早发性共济失调的临床表现和诊断挑战

A 16-year-old adolescent girl presented with progressive walking imbalance, uncoordination of her limbs, impaired proprioceptive sensation distal to her wrists and ankles, and sensorineural hearing loss. Her evaluation revealed diffuse cerebellar atrophy, a demyelinating neuropathy, and hypergonadotropic hypogonadism. In this article, we present a systematic approach to a patient with early-onset ataxia, cerebellar atrophy, and demyelinating neuropathy.

一名16岁的青春期女孩表现出进行性行走不平衡，四肢不协调，手腕和脚踝远端的本体感觉受损以及感觉神经性听力损失。她的评估显示弥漫性小脑萎缩，脱髓鞘性神经病和高促性腺激素性性腺功能减退症。在本文中，我们为患有早发性共济失调，小脑萎缩和脱髓鞘性神经病的患者提供了一种系统的方法。

REF: Chadha D, Viswanathan LG, Santhoshkumar R, et al. Clinical Reasoning: Clinical Manifestations and Diagnostic Challenges in a 16-Year-Old With Early-Onset Ataxia. Neurology. 2025;104(2):e210253. doi:10.1212/WNL.0000000000210253 PMID: 39729613

Challenges in Describing Tremor and Dystonia

描述震颤和肌张力障碍的挑战

Tremor is defined as an oscillatory and rhythmical movement. By contrast, dystonia is defined by sustained or intermittent abnormal postures, repetitive movements, or both. Tremor and dystonia often coexist in the same individual. Sometimes tremor and dystonia occur in the same body region, and sometimes they occur in separate body regions. In other cases, dystonic movements are rapid and repetitive, and they may mimic tremor. The varied clinical phenomenology of dystonia and tremor were recognized in the earliest descriptions of dystonia, and various terms have been used to describe the relationships between tremor and dystonia. The term dystonic tremor was first introduced to distinguish tremor-like movements in dystonia from more common tremors such as essential tremor. Subsequently, the same term was adopted to refer to any combination of dystonia and tremor in the same body region. Both applications of this term continue to be used in the modern literature. Other related terms have also been proposed such as tremor associated with dystonia, tremulous dystonia, dystonia-tremor syndrome, and dystonia with tremor. The proliferation of terms has become confusing, and expert opinion regarding application of these terms is divided, so a group of specialists was assembled to review the terminology and to develop recommendations for a more consistent approach. The group agreed that the term tremor should exclusively refer to rhythmic movements. The group also agreed that repetitive dystonic movements that are grossly arrhythmic should not be labeled with terms that imply they are a type of tremor. Moreover, when tremor and dystonia coexist, it may be clinically more useful to describe them separately, using descriptive terms rather than hybrid terms that imply suspected etiology. Easy-to-use clinical terms are essential, although bedside discrimination of movements may sometimes be challenging. In the future, motion analysis or physiologic measures may aid in the discrimination of movements that remain clinically uncertain.

震颤被定义为振荡和有节奏的运动。相比之下，肌张力障碍由持续或间歇性异常姿势、重复运动或两者定义。震颤和肌张力障碍经常在同一个体中共存。有时震颤和肌张力障碍发生在同一身体区域，有时它们发生在不同的身体区域。在其他情况下，肌张力障碍运动是快速且重复的，并且它们可能模仿震颤。肌张力障碍和震颤的各种临床现象在肌张力障碍的最早描述中得到认可，并且各种术语已用于描述震颤和肌张力障碍之间的关系。首先引入术语肌张力障碍性震颤是为了将肌张力障碍中的震颤样运动与更常见的震颤 (例如特发性震颤) 区分开。随后，采用相同的术语来指代相同身体区域中的肌张力障碍和震颤的任何组合。该术语的两个应用程序在现代文学中继续使用。还提出了其他相关术语，例如与肌张力障碍相关的震颤，震颤性肌张力障碍，肌张力障碍-震颤综合征和肌张力障碍伴震颤。术语的激增变得令人困惑，关于这些术语的应用的专家意见也存在分歧，因此召集了一组专家来审查术语并为更一致的方法提出建议。该小组同意，震颤一词应仅指有节奏的运动。该小组还同意，严重心律失常的重复性肌张力障碍运动不应标有暗示它们是一种震颤的术语。此外，当震颤和肌张力障碍共存时，使用描述性术语而不是暗示可疑病因的混合术语分别描述它们可能在临床上更有用。易于使用的临床术语是必不可少的，尽管床边对运动的辨别有时可能具有挑战性。将来，运动分析或生理测量可能有助于区分临床上仍不确定的运动。

REF: Shaikh AG, Fasano A, Pandey S, et al. Challenges in Describing Tremor and Dystonia. Neurology. 2025;104(2):e210209. doi:10.1212/WNL.0000000000210209 PMID: 39724539

Blood-Based Biomarkers and Risk of Onset of Mild Cognitive Impairment Over the Short and Long Term

基于血液的生物标志物和短期和长期轻度认知障碍发作的风险

Blood-based biomarkers of amyloid and tau have been shown to predict Alzheimer disease (AD) dementia. Much less is known about their ability to predict risk of mild cognitive impairment (MCI), an earlier disease stage. This study examined whether levels of blood biomarkers of amyloid (Aβ42/Aβ40ratio), tau (p-tau181), neurodegeneration (NfL), and glial activation and neuroinflammation (glial fibrillary acidic protein [GFAP], YKL40, soluble triggering receptor expressed on myeloid cells 2 [sTREM2]) collected when participants were cognitively normal are associated with the time to onset of MCI. Results indicate that during preclinical AD, more abnormal blood biomarker levels of amyloid (Aβ42/Aβ40), p-tau181, neurodegeneration (NfL), and neuroinflammation (GFAP) individually are associated with progression from normal cognition to MCI, but the AD-nonspecific neurodegeneration and inflammation markers were not associated with symptom onset after accounting for amyloid and p-tau levels.

基于血液的淀粉样蛋白和tau蛋白生物标志物已被证明可以预测阿尔茨海默病 (AD) 痴呆。关于他们预测早期疾病阶段轻度认知障碍 (MCI) 风险的能力知之少。这项研究检查了淀粉样蛋白 (Aβ42/aβ40比例)，tau (p-tau181)，神经变性 (NfL) 以及神经胶质活化和神经炎症 (胶质纤维酸性蛋白 [GFAP]，YKL40，髓样细胞表达的可溶性触发受体2 [sTREM2]) 的血液生物标志物水平当参与者认知正常时收集的数据与MCI发作的时间相关。结果表明，在临床前AD期间，淀粉样蛋白 (Aβ42/Aβ40)，p-tau181，神经变性 (NfL) 和神经炎症 (GFAP) 的异常血液生物标志物水平分别与从正常认知到MCI的进展有关。但是，在考虑淀粉样蛋白和p-tau水平后，AD非特异性神经变性和炎症标志物与症状发作无关。

REF: Soldan A, Pettigrew C, Wang J, et al. Blood-Based Biomarkers and Risk of Onset of Mild Cognitive Impairment Over the Short and Long Term. Neurology. 2025;104(2):e210225. doi:10.1212/WNL.0000000000210225 PMID: 39724536