Distinct Alterations of Inflammatory Biomarkers in Cluster Headache: A Case Control Study

丛集性头痛中炎症生物标志物的明显改变：一项病例对照研究

Investigate the immune system's role in cluster headache by analyzing cytokines in people with cluster headache and headache-free controls, and explore if certain cytokines could predict a specific phenotype. Findings show that the immune system is altered in all 3 states of cluster headache compared with controls. Oncostatin m was elevated, constituting a promising target for future studies. The distinct alterations between episodic and chronic cluster headache are striking and urges further research of the immune system in cluster headache to better understand its potential role in prediction of disease activity and treatment response.

通过分析丛集性头痛患者和无头痛对照组人群的细胞因子，研究免疫系统在丛集性头痛中的作用，并探究某些细胞因子是否可以预测特定表型。研究结果显示，与对照组相比，丛集性头痛的所有三种状态下免疫系统均发生了改变。抑瘤素M水平升高，这为未来的研究提供了一个有前景的靶点。发作性和慢性丛集性头痛之间存在明显的差异，这迫切需要进一步研究丛集性头痛中的免疫系统，以更好地了解其在预测疾病活动和治疗反应方面的潜在作用。

REF: Lund NLT, Westgate CSJ, Søborg MK, et al. Distinct Alterations of Inflammatory Biomarkers in Cluster Headache: A Case Control Study. Ann Neurol. 2025;98(1):4-18. doi:10.1002/ana.27205 PMID: 39981939 PMCID: PMC12174737

Longitudinal Metabolomics in Amyotrophic Lateral Sclerosis Implicates Impaired Lipid Metabolism

肌萎缩侧索硬化症的纵向代谢组学研究提示脂质代谢受损

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by altered metabolome and energy homeostasis, manifesting with body mass index changes and hypermetabolism-both prognostic of disease progression and survival. The cross-sectional ALS metabolome has been characterized, but longitudinal correlations to functional decline are lacking. Our findings suggest metabolomic changes primarily involving different lipid classes and carnitine metabolism may underscore ALS severity and progression.

肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是代谢组和能量稳态改变，表现为体重指数变化和代谢亢进，这两者均与疾病进展和生存预后相关。目前已对肌萎缩侧索硬化症的横断面代谢组进行了表征，但缺乏与功能衰退的纵向相关性研究。我们的研究结果表明，主要涉及不同脂质类别和肉碱代谢的代谢组学变化可能是肌萎缩侧索硬化症严重程度和进展的基础。

REF: Guo K, Savelieff MG, Jang DG, et al. Longitudinal Metabolomics in Amyotrophic Lateral Sclerosis Implicates Impaired Lipid Metabolism. Ann Neurol. 2025;98(1):19-34. doi:10.1002/ana.27208 PMID: 39976286 PMCID: PMC12174748

Psychoses of Epilepsy: Unravelling the Phenotypic and Genotypic Features

癫痫性精神病：揭示表型和基因型特征

We analyzed the genotypic and phenotypic features of patients with psychosis of epilepsy (POE). Interictal POE is threefold more common than PIP, and more likely to be associated with both rare pathogenic variants for epilepsy and common risk variants for schizophrenia. Distinguishing between different POE phenotypes enhances clinical practice and our understanding of etiology, paving the way for precision medicine.

我们分析了癫痫性精神病（POE）患者的基因型和表型特征。发作间期癫痫性精神病的常见程度是发作期癫痫性精神病的三倍，且更有可能与癫痫的罕见致病变异和精神分裂症的常见风险变异相关。区分不同的癫痫性精神病表型有助于改善临床实践，加深我们对病因的理解，为精准医学铺平道路。

REF: Rayner G, Honybun E, Bahlo M, Oliver KL, Scheffer IE. Psychoses of Epilepsy: Unravelling the Phenotypic and Genotypic Features. Ann Neurol. 2025;98(1):35-47. doi:10.1002/ana.27209 PMID: 39950246 PMCID: PMC12174738

Fluoxetine Treatment in Epilepsy of Infancy with Migrating Focal Seizures Due to KCNT1 Variants: An Open Label Study

氟西汀治疗KCNT1基因变异所致婴儿期游走性局灶性发作癫痫：一项开放性标签研究

Gain-of-function (GoF) variants in KCNT1 encoding for potassium channels are associated with different epilepsy phenotypes, including epilepsy of infancy with migrating focal seizures (EIMFS), other early infantile developmental and epileptic encephalopathies, and focal epilepsy. Fluoxetine blocks currents from both wild-type (WT) and mutant KCNT1 channels with GoF in vitro features. In this study, we tested the hypothesis that treatment with fluoxetine might improve clinical outcome in patients with EIMFS carrying GoF variants in KCNT1 channels showing in vitro sensitivity to fluoxetine blockade. Fluoxetine may be a potential targeted medication in EIMFS caused by KCNT1 GoF variants. Further research is needed to assess its long-term efficacy and safety.

编码钾通道的KCNT1基因功能获得性（GoF）变异与不同的癫痫表型相关，包括伴游走性局灶性发作的婴儿癫痫（EIMFS）、其他早发性婴儿发育性和癫痫性脑病以及局灶性癫痫。氟西汀在体外能阻断野生型（WT）和具有功能获得性特征的突变型KCNT1通道的电流。在本研究中，我们验证了以下假设：对于携带对氟西汀阻断作用具有体外敏感性的KCNT1通道功能获得性变异的EIMFS患者，使用氟西汀治疗可能改善其临床结局。氟西汀可能是由KCNT1功能获得性变异导致的EIMFS的一种潜在靶向药物。需要进一步研究来评估其长期疗效和安全性。

REF: Trivisano M, Mosca I, Salimbene L, et al. Fluoxetine Treatment in Epilepsy of Infancy with Migrating Focal Seizures Due to KCNT1 Variants: An Open Label Study. Ann Neurol. 2025;98(1):48-61. doi:10.1002/ana.27213 PMID: 39981956 PMCID: PMC12174750

Cognitive Outcome in Young Adults after Resolution of Epilepsy in Childhood

儿童期癫痫缓解后年轻成年人的认知结局

Self-limited epilepsies of childhood are common and were considered benign. We aim to determine whether cognitive function in young adults who experienced epilepsy as children and are subsequently seizure-free and unmedicated differ from the general population. We report on a cross-sectional population-based study including 2,124,871 men and women aged 16-19 years. Participants > 5 years following the last seizure and > 2 years without anti-seizure medication (n = 3,452) had an odds ratio (OR) of having low cognitive function of 1.44 (95% confidence interval [CI] = 1.24-1.68, p < 0.001) using a multinominal regression model. Our results underscore the need to avoid the term "benign" in the classification of childhood epilepsies.

儿童自限性癫痫很常见，过去曾被认为是良性的。我们旨在确定儿童时期患过癫痫、随后无发作且未用药的年轻人的认知功能是否与普通人群存在差异。我们报告了一项基于人群的横断面研究，该研究纳入了2124871名年龄在16 - 19岁的男性和女性。末次发作后超过5年且停用抗癫痫药物超过2年的参与者（n = 3452），通过多项逻辑回归模型分析发现，其出现低认知功能的比值比（OR）为1.44（95%置信区间[CI] = 1.24 - 1.68，p < 0.001）。我们的研究结果强调，在儿童癫痫分类中应避免使用“良性”这一术语。

REF: Megreli J, Arkush L, Derazne E, et al. Cognitive Outcome in Young Adults after Resolution of Epilepsy in Childhood. Ann Neurol. 2025;98(1):62-66. doi:10.1002/ana.27258 PMID: 40401928 PMCID: PMC12174746

Mapping Molecular Pathways of Multiple Sclerosis: A Gene Prioritization and Network Analysis of White Matter Pathology Transcriptomics

绘制多发性硬化症的分子通路图谱：白质病理转录组学的基因优先级排序与网络分析

Rapid advances in transcriptomics have driven efforts to identify deregulated pathways in multiple sclerosis (MS) tissues, though many detected differentially expressed genes are likely false positives, with only a small fraction reflecting actual pathological events. Robust, integrative methods are essential for accurately understanding the molecular mechanisms underlying MS pathology. Our strategy provides a robust framework for integrating gene expression data, effectively identifying the intricate pathways altered in human diseased tissues. This method holds potential for translating findings into drug development strategies.

转录组学的快速发展推动了在多发性硬化症（MS）组织中识别失调通路的研究，不过许多检测到的差异表达基因可能是假阳性结果，只有一小部分反映了实际的病理事件。可靠的整合方法对于准确理解MS病理背后的分子机制至关重要。我们的策略为整合基因表达数据提供了一个可靠的框架，能够有效识别人类患病组织中发生改变的复杂通路。这种方法有望将研究成果转化为药物研发策略。

REF: Abbadessa G, Nagano A, Hametner S, et al. Mapping Molecular Pathways of Multiple Sclerosis: A Gene Prioritization and Network Analysis of White Matter Pathology Transcriptomics. Ann Neurol. 2025;98(1):67-79. doi:10.1002/ana.27216 PMID: 39949311 PMCID: PMC12174739

Efficacy and Safety of Ofatumumab Treatment for Anti-NMDA Receptor Autoimmune Encephalitis (OFF-AE): A Prospective, Multicenter Cohort Study

奥法木单抗治疗抗 N - 甲基 - D - 天冬氨酸受体自身免疫性脑炎的有效性和安全性（OFF - AE）：一项前瞻性、多中心队列研究

Ofatumumab presents a potentially promising alternative to current second-line immunotherapy for refractory anti-N-methyl-D-aspartate receptor autoimmune encephalitis (NMDAR-AE). We aimed to evaluate the efficacy and safety of ofatumumab as a novel second-line immunotherapy for NMDAR-AE. Ofatumumab showed substantial efficacy and safety, particularly in patients who failed first-line immunotherapy, warranting its consideration in NMDAR-AE management.

奥法木单抗为难治性抗N-甲基-D-天冬氨酸受体自身免疫性脑炎（NMDAR - AE）的现有二线免疫治疗提供了一种潜在的有前景的替代方案。我们旨在评估奥法木单抗作为NMDAR - AE新型二线免疫治疗的有效性和安全性。奥法木单抗显示出显著的有效性和安全性，尤其对于一线免疫治疗失败的患者，因此在NMDAR - AE的治疗中值得考虑使用该药物。

REF: Guo K, Peng F, Liu J, et al. Efficacy and Safety of Ofatumumab Treatment for Anti-NMDA Receptor Autoimmune Encephalitis (OFF-AE): A Prospective, Multicenter Cohort Study. Ann Neurol. 2025;98(1):80-92. doi:10.1002/ana.27218 PMID: 39991981

Clinical, Prognostic, and Longitudinal Functional and Neuropsychological Features of West Nile Virus Neuroinvasive Disease in the United States: A Systematic Review and Meta-Analysis

美国西尼罗河病毒神经侵袭性疾病的临床、预后、纵向功能及神经心理学特征：系统评价与荟萃分析

West Nile virus (WNV) is the most common cause of arboviral disease in the United States. Approximately 1% of infections involve the nervous system, most commonly resulting in West Nile encephalitis (WNE), West Nile meningitis (WNM), or acute flaccid paralysis (AFP). The findings underscore the significant mortality and morbidity of WNND in the acute and long-term setting. Our findings may additionally provide utility for risk stratification of hospitalized patients with WNND and suggest the need for further evaluation of novel therapeutics to prevent substantial disease-associated acute and long-term disability.

西尼罗河病毒（WNV）是美国虫媒病毒病最常见的病因。约1%的感染会累及神经系统，最常见的表现为西尼罗河脑炎（WNE）、西尼罗河脑膜炎（WNM）或急性弛缓性麻痹（AFP）。这些研究结果凸显了西尼罗河神经侵袭性疾病（WNND）在急性期和长期阶段所导致的显著死亡率和发病率。我们的研究结果可能还对住院的WNND患者进行风险分层有帮助，并提示需要进一步评估新型疗法，以预防与该病相关的严重急性和长期残疾。

REF: Roberts JA, Kim CY, Hwang SA, et al. Clinical, Prognostic, and Longitudinal Functional and Neuropsychological Features of West Nile Virus Neuroinvasive Disease in the United States: A Systematic Review and Meta-Analysis. Ann Neurol. 2025;98(1):93-106. doi:10.1002/ana.27220 PMID: 40008684

Blood DDIT4 and TRIM13 Transcript Levels Mark the Early Stages of Machado–Joseph Disease

血液中DDIT4和TRIM13转录水平可作为马查多 - 约瑟夫病早期阶段的标志物

An abundance of select transcripts and proteins has been found to be dysregulated in blood samples of Machado-Joseph disease (MJD) carriers. Here, we aimed to: (1) identify blood transcriptional changes as potential biomarkers of MJD; (2) correlate levels of differentially expressed blood transcripts with MJD carriers features; and (3) evaluate whether the identified differential abundance of blood transcripts in MJD patients is preserved in MJD brains. Overall, blood DDIT4 and TRIM13 transcript levels are potential biomarkers of MJD. Cellular processes involving DDIT4, TRIM13, and P2RY13 appear to be commonly dysregulated in the blood and brain of MJD patients, indicating the involvement of these genes in MJD pathogenesis.

在 Machado - Joseph 病（MJD）携带者的血液样本中，发现大量特定的转录本和蛋白质存在表达失调的情况。在此，我们的目标是：（1）确定血液转录变化，将其作为 MJD 的潜在生物标志物；（2）将差异表达的血液转录本水平与 MJD 携带者的特征相关联；（3）评估在 MJD 患者血液中鉴定出的转录本差异丰度是否在 MJD 患者的大脑中也存在。总体而言，血液中 DDIT4 和 TRIM13 转录本水平是 MJD 的潜在生物标志物。涉及 DDIT4、TRIM13 和 P2RY13 的细胞过程在 MJD 患者的血液和大脑中似乎普遍存在表达失调，这表明这些基因参与了 MJD 的发病机制。

REF: Ferreira AF, Raposo M, Shaw ED, et al. Blood DDIT4 and TRIM13 Transcript Levels Mark the Early Stages of Machado-Joseph Disease. Ann Neurol. 2025;98(1):107-119. doi:10.1002/ana.27222 PMID: 40041945 PMCID: PMC12174760