Paraneoplastic Neurologic Syndromes Associated With Merkel Cell Carcinoma

与Merkel细胞癌相关的副肿瘤神经系统综合征

To define the clinical and immunologic profile of patients with paraneoplastic neurologic syndromes (PNSs) associated with Merkel cell carcinoma (MCC). Retrospective analysis was conducted on patients with suspected MCC-related PNS assessed at the French Reference Center, and cases were identified by a systematic review of the literature (MEDLINE, Embase) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MCC-related PNSs present as a heterogeneous clinical spectrum including central and/or peripheral nervous system disorders such as LEMS, RCPS, and EM, mainly associated with VGCC-Abs, NF-Abs, and Hu-Abs. NF-Abs were only seen among patients with CNS disorders. At onset, the absence of a primary skin tumor but presence of lymph node metastasis is frequently observed, and this particular clinical presentation is linked to reduced mortality, highlighting distinctive clinical and immunologic features of MCC-related PNS.

确定与Merkel细胞癌 (MCC) 相关的副肿瘤神经系统综合征 (PNSs) 患者的临床和免疫学特征。对在法国参考中心评估的疑似MCC相关PNS患者进行回顾性分析，并根据系统综述和荟萃分析指南的首选报告项目，通过文献系统综述 (MEDLINE，Embase) 确定病例。MCC相关的PNSs作为异质临床谱存在，包括中枢和/或外周神经系统疾病，例如LEMS、RCPS和EM，主要与vgcc-abs、nf-abs和hu-abs相关。Nf-abs仅见于中枢神经系统疾病患者。发病时，经常观察到没有原发性皮肤肿瘤，但存在淋巴结转移，这种特殊的临床表现与死亡率降低有关，突出了MCC相关PNS的独特临床和免疫学特征。

REF: Ciano-Petersen NL, Muñiz-Castrillo S, Villagrán-García M, et al. Paraneoplastic Neurologic Syndromes Associated With Merkel Cell Carcinoma. Neurol Neuroimmunol Neuroinflamm. 2024;11(6):e200260. doi:10.1212/NXI.0000000000200260 PMID: 39388653

Retinal Damage and Visual Network Reconfiguration Defines Visual Function Recovery in Optic Neuritis

视网膜损伤和视觉网络重构定义视神经炎的视觉功能恢复

Recovery of vision after acute optic neuritis (AON) is critical to improving the quality of life of people with demyelinating diseases. The objective of the study was to prospectively assess the changes in visual acuity, retinal layer thickness, and cortical visual network in patients with AON to identify the predictors of permanent visual disability. The assessment of the visual pathway at baseline predicts permanent vision disability after AON, indicating that damage is produced early after disease onset and that it can be used for defining vision impairment and guiding therapy.

急性视神经炎 (AON) 后的视力恢复对于改善脱髓鞘疾病患者的生活质量至关重要。该研究的目的是前瞻性评估AON患者的视力，视网膜层厚度和皮质视觉网络的变化，以确定永久性视力障碍的预测因素。基线视觉通路的评估可预测AON后的永久性视力残疾，表明损伤是在疾病发作后的早期产生的，并且可用于定义视力障碍和指导治疗。

REF: Villoslada P, Solana E, Alba-Arbalat S, et al. Retinal Damage and Visual Network Reconfiguration Defines Visual Function Recovery in Optic Neuritis. Neurol Neuroimmunol Neuroinflamm. 2024;11(6):e200288. doi:10.1212/NXI.0000000000200288 PMID: 39213469

Diagnostic Value of Inter-Eye Difference Metrics on OCT for Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis

OCT眼间差异指标对髓鞘少突胶质细胞糖蛋白抗体相关性视神经炎的诊断价值

The 2022 International Consortium for Optic Neuritis diagnostic criteria for optic neuritis (ON) include optical coherence tomography (OCT). The diagnostic value of intereye difference (IED) metrics is high for ON in patients with multiple sclerosis and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders, but unknown in myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON). A multicenter validation study was conducted on the published IED cutoff values (>4% or >4 μm in the macular ganglion cell and inner plexiform layer [mGCIP] or >5% or >5 μm in the peripapillary retinal nerve fiber layer [pRNFL]) in individuals with MOG-ON and age-matched and sex-matched healthy controls (HCs). In individuals with MOG-ON, the diagnostic accuracy of OCT-based IED metrics for ON was high, especially of mGCIP IEPD. This study provides Class III evidence that the intereye difference on OCT can distinguish between those with MOG and normal controls.

2022国际视神经炎联合会视神经炎 (ON) 的诊断标准包括光学相干断层扫描 (OCT)。眼间差异 (IED) 指标对多发性硬化症和aquaporin-4抗体阳性视神经脊髓炎谱系疾病患者的诊断价值很高，但在髓磷脂少突胶质细胞糖蛋白抗体相关ON (MOG-ON) 中未知。对已公布的IED临界值 (黄斑神经节细胞和内丛状层> 4% 或> 4 μ m [mGCIP] 或乳头周围视网膜神经纤维层> 5% 或> 5 μ m [pRNFL]) 进行多中心验证研究在具有mog-on和年龄匹配和性别匹配的健康对照 (HCs) 的个体中。在患有mog-on的个体中，基于OCT的IED指标对ON的诊断准确性很高，尤其是mGCIP IEPD。这项研究提供了III类证据，表明OCT的眼间差异可以区分MOG和正常对照。

REF: Volpe G, Jurkute N, Girafa G, et al. Diagnostic Value of Inter-Eye Difference Metrics on OCT for Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis. Neurol Neuroimmunol Neuroinflamm. 2024;11(6):e200291. doi:10.1212/NXI.0000000000200291 PMID: 39231384

Advanced Quantitative MRI Unveils Microstructural Thalamic Changes Reflecting Disease Progression in Multiple Sclerosis

先进的定量MRI揭示了反映多发性硬化症疾病进展的显微结构丘脑变化

In patients with multiple sclerosis (PwMS), thalamic atrophy occurs during the disease course. However, there is little understanding of the mechanisms leading to volume loss and of the relationship between microstructural thalamic pathology and disease progression. This cross-sectional and longitudinal study aimed to comprehensively characterize in vivo pathologic changes within thalamic microstructure in PwMS using advanced multiparametric quantitative MRI (qMRI). Thalamic microstructural integrity was evaluated using quantitative T1, magnetization transfer saturation, multishell diffusion, and quantitative susceptibility mapping (QSM) in 183 PwMS and 105 healthy controls (HCs). These findings offer deeper insights into thalamic pathology in PwMS, emphasizing the clinical relevance of thalamic damage and its link to disease progression. Advanced qMRI biomarkers show promising potential in guiding interventions aimed at mitigating thalamic neurodegenerative processes.

在多发性硬化症 (PwMS) 患者中，丘脑萎缩在疾病过程中发生。然而，对于导致体积损失的机制以及丘脑微结构病理与疾病进展之间的关系知之甚少。这项横断面和纵向研究旨在使用先进的多参数定量MRI (qMRI) 全面表征PwMS丘脑微结构内的体内病理变化。在183 pwm和105健康对照 (hc) 中，使用定量T1，磁化转移饱和度，多壳层扩散和定量磁化率映射 (QSM) 评估了丘脑的微观结构完整性。这些发现为PwMS的丘脑病理提供了更深入的见解，强调了丘脑损伤的临床相关性及其与疾病进展的联系。先进的qMRI生物标志物在指导旨在减轻丘脑神经退行性过程的干预方面显示出有希望的潜力。

REF: Cagol A, Ocampo-Pineda M, Lu PJ, et al. Advanced Quantitative MRI Unveils Microstructural Thalamic Changes Reflecting Disease Progression in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2024;11(6):e200299. doi:10.1212/NXI.0000000000200299 PMID: 39270143

CSF Parvalbumin Levels at Multiple Sclerosis Diagnosis Predict Future Worse Cognition, Physical Disability, Fatigue, and Gray Matter Damage

多发性硬化诊断时CSF小白蛋白水平可预测未来更差的认知，身体残疾，乏力和灰质损伤

Cognitive impairment (CI) in multiple sclerosis (MS) is frequent and determined by a complex interplay between inflammatory and neurodegenerative processes. We aimed to investigate whether CSF parvalbumin (PVALB), measured at the time of diagnosis, may have a prognostic role in patients with MS. In this cohort study, CSF analysis of PVALB and Nf-L levels was performed on all patients at diagnosis (T0) and combined with physical, cognitive, and MRI assessment after an average of 4 years of follow-up (T4) from diagnosis. The significant association found between parvalbumin levels in the CSF at diagnosis and cognitive, clinical, and neuroradiologic worsening after 4 years of follow-up support the idea that parvalbumin, in addition to Nf-L, might represent a new potential prognostic biomarker, reflecting MS neurodegenerative processes occurring since early disease stages.

多发性硬化症 (MS) 中的认知障碍 (CI) 是常见的，并且由炎症和神经变性过程之间的复杂相互作用决定。我们旨在调查在诊断时测量的CSF小白蛋白 (PVALB) 是否可能对MS患者具有预后作用。在这项队列研究中，对所有患者在诊断时 (T0) 进行PVALB和nf-i水平的CSF分析，并结合身体，认知，并从诊断后平均随访4年 (T4) 进行MRI评估。在4年的随访后，诊断时CSF中的小白蛋白水平与认知，临床和神经放射学恶化之间存在显着关联，这支持了这样的观点，即小白蛋白除了nf-i外，可能还代表了一种新的潜在预后生物标志物，反映了自疾病早期以来发生的MS神经退行性疾病过程。

REF: Ziccardi S, Tamanti A, Ruggieri C, et al. CSF Parvalbumin Levels at Multiple Sclerosis Diagnosis Predict Future Worse Cognition, Physical Disability, Fatigue, and Gray Matter Damage. Neurol Neuroimmunol Neuroinflamm. 2024;11(6):e200301. doi:10.1212/NXI.0000000000200301 PMID: 39178066

Impact of the Multiple Sclerosis-Associated Genetic Variant CD226 Gly307Ser on Human CD8 T-Cell Functions

多发性硬化相关遗传变异CD226 Gly307Ser对人CD8 T细胞功能的影响

The rs763361 nonsynonymous variant in the CD226 gene, which results in a glycine-to-serine substitution at position 307 of the CD226 protein, has been implicated as a risk factor of various immune-mediated diseases, including multiple sclerosis (MS). Compelling evidence suggests that this allele may play a significant role in predisposing individuals to MS by decreasing the immune-regulatory capacity of Treg cells and increasing the proinflammatory potential of effector CD4 T cells. However, the impact of this CD226 gene variant on CD8 T-cell functions, a population that also plays a key role in MS, remains to be determined. Our data suggest that the CD226-307Ser risk variant imposes immune dysregulation by increasing the pathways related to IFNγ signaling in CD8 T cells, thereby contributing to the risk of developing chronic inflammation.

CD226基因中的rs763361非同义变体导致CD226蛋白的位置307处的甘氨酸至丝氨酸取代，已被认为是各种免疫介导的疾病 (包括多发性硬化症 (MS)) 的危险因素。令人信服的证据表明，该等位基因可能通过降低Treg细胞的免疫调节能力和增加效应CD4 T细胞的促炎潜力，在使个体易患MS方面发挥重要作用。然而，这种CD226基因变体对CD8 T细胞功能的影响仍有待确定，CD8 T细胞功能在MS中也起着关键作用。我们的数据表明，CD226-307Ser风险变体通过增加CD8 T细胞中与ifn γ 信号传导相关的途径来施加免疫失调，从而导致发生慢性炎症的风险。

REF: Morandi E, Adoue V, Bernard I, et al. Impact of the Multiple Sclerosis-Associated Genetic Variant CD226 Gly307Ser on Human CD8 T-Cell Functions. Neurol Neuroimmunol Neuroinflamm. 2024;11(6):e200306. doi:10.1212/NXI.0000000000200306 PMID: 39231385

A Simple Score (MOG-AR) to Identify Individuals at High Risk of Relapse After MOGAD Attack

一个简单的分数 (mog-ar)，以确定在MOGAD攻击后复发的高风险个体

To identify predictors for relapse in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to develop and validate a simple risk score for predicting relapse. In China National Registry of Neuro-Inflammatory Diseases (CNRID), we identified patients with MOGAD from March 2023 and followed up prospectively to September 2023. The risk of MOGAD relapse seems to be predictable. Further validation of MOG-AR score developed from this cohort to determine appropriate treatment and monitoring frequency is warranted. CNRID, NCT05154370, registered December 13, 2021, first enrolled December 15, 2021.

确定髓鞘少突胶质细胞糖蛋白抗体相关疾病 (MOGAD) 患者复发的预测因子，并开发和验证预测复发的简单风险评分。在中国国家神经炎性疾病注册中心 (CNRID) 中，我们确定了2023 3月以来的MOGAD患者，并前瞻性随访至2023年9月。MOGAD复发的风险似乎是可预测的。需要进一步验证从该队列开发的mog-ar评分，以确定适当的治疗和监测频率。CNRID，NCT05154370，于2021年12月13日注册，于2021年12月15日首次注册。

REF: Xu Y, Meng H, Fan M, et al. A Simple Score (MOG-AR) to Identify Individuals at High Risk of Relapse After MOGAD Attack. Neurol Neuroimmunol Neuroinflamm. 2024;11(6):e200309. doi:10.1212/NXI.0000000000200309 PMID: 39250723

IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study

特发性REM睡眠行为障碍中的IGLON5频率: 一项多中心研究

Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD. Our finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings. NCT03623672.

特发性/孤立的REM睡眠行为障碍 (iRBD) 与神经退行性突触核蛋白病密切相关，例如帕金森病，路易体痴呆和多系统萎缩。然而，越来越多的报道将RBD作为严重和可治疗的自身免疫综合征，特别是iglon5的表现特征。这项研究的目的是调查大型iRBD参与者中自身抗体的频率。我们的发现是，近1% 的大型iRBD队列可能患有严重但可治疗的自身抗体综合征，这具有重要的临床意义。特别是，它提出了一个问题，即考虑到自身免疫性疾病的诊断困难，对治疗的反应以及疾病快速进展的潜力，是否应对IGLON-5-IgG的参与者广泛实施iRBD的自身抗体检测。然而，任何常规测试方案也必须考虑成本和假阳性结果的潜在不利影响。Nct03623672。

REF: Postuma R, Vorasoot N, St Louis EK, et al. IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study. Neurol Neuroimmunol Neuroinflamm. 2024;11(6):e200311. doi:10.1212/NXI.0000000000200311 PMID: 39270144

Multiple Sclerosis Patient Macrophages Impaired Metabolism Leads to an Altered Response to Activation Stimuli

多发性硬化症患者巨噬细胞代谢受损导致对激活刺激的反应改变

In multiple sclerosis (MS), immune cells invade the CNS and destroy myelin. Macrophages contribute to demyelination and myelin repair, and their role in each process depends on their ability to acquire specific phenotypes in response to external signals. In this article, we assess whether defects in MS patient macrophage responses may lead to increased inflammation or lack of neuroregenerative effects. CD14+CD16- monocytes from patients with MS and healthy controls (HCs) were activated in vitro to obtain homeostatic-like, proinflammatory, and proregenerative macrophages. Our results show an intrinsic defect of MS patient macrophages, reminiscent of innate immune cell memory in MS, lifting macrophage importance in the disease and as potential therapeutic targets.

在多发性硬化症 (MS) 中，免疫细胞侵入CNS并破坏髓磷脂。巨噬细胞有助于脱髓鞘和髓鞘修复，它们在每个过程中的作用取决于它们响应外部信号获得特定表型的能力。在本文中，我们评估了MS患者巨噬细胞反应的缺陷是否可能导致炎症增加或缺乏神经再生作用。来自MS患者和健康对照 (hc) 的CD14 CD16-单核细胞在体外被激活，以获得稳态样，促炎性和促再生的巨噬细胞。我们的结果显示MS患者巨噬细胞的内在缺陷，让人联想到MS中的先天免疫细胞记忆，提升了巨噬细胞在疾病中的重要性并作为潜在的治疗靶标。

REF: Fransson J, Bachelin C, Ichou F, et al. Multiple Sclerosis Patient Macrophages Impaired Metabolism Leads to an Altered Response to Activation Stimuli. Neurol Neuroimmunol Neuroinflamm. 2024;11(6):e200312. doi:10.1212/NXI.0000000000200312 PMID: 39467238