MOG CNS Autoimmunity and MOGAD

MOG CNS自身免疫和MOGAD

At one time considered a possible form of neuromyelitis optica (NMO) spectrum disorder (NMOSD), it is now accepted that myelin oligodendrocyte glycoprotein (MOG) antibody (Ab)-associated disorder (MOGAD) is a distinct entity from either NMO or multiple sclerosis (MS) and represents a broad spectrum of clinical phenotypes. Key insights in neuroimmunology and MOGAD pathogenesis have been learned from MOG experimental autoimmune encephalomyelitis (EAE), described 2 decades before the term MOGAD was introduced. Understanding both the humoral and cellular immunology of MOGAD has implications for diagnosis, treatment, and prognosis.

曾经被认为是视神经脊髓炎 (NMO) 谱系障碍 (NMOSD) 的一种可能形式，现在人们认为髓磷脂少突胶质细胞糖蛋白 (MOG) 抗体 (Ab) 相关疾病 (MOGAD) 是与NMO或多发性硬化症 (MS) 不同的实体并代表了广泛的临床表型。从MOG实验性自身免疫性脑脊髓炎 (EAE) 中了解到神经免疫学和MOGAD发病机理的关键见解，该术语在引入MOGAD之前已有20年的描述。了解MOGAD的体液和细胞免疫学对诊断，治疗和预后具有重要意义。

REF: Moseley CE, Virupakshaiah A, Forsthuber TG, Steinman L, Waubant E, Zamvil SS. MOG CNS Autoimmunity and MOGAD. Neurol Neuroimmunol Neuroinflamm. 2024;11(5):e200275. doi:10.1212/NXI.0000000000200275 PMID: 38996203

A 73-Year-Old Woman With Confusion, Visual Field Disturbances, and Edematous White Matter Lesions: From the National Multiple Sclerosis Society Case Conference Proceedings

一名73岁的妇女，患有混乱，视野障碍和水肿性白质病变: 来自国家多发性硬化症协会病例会议记录

We describe the case of a 73-year-old woman presenting with headaches, confusion, and vision disturbances. Brain MRI showed a large T2-hyperintense lesion in the right temporo-occipital region with vasogenic edema and leptomeningeal enhancement. A leptomeningeal biopsy was performed, which led to a definitive diagnosis.

我们描述了一名73岁的女性出现头痛，混乱和视力障碍的情况。脑MRI显示右颞枕区有较大的T2-hyperintense病变，伴有血管源性水肿和软脑膜增强。进行了软脑膜活检，这导致了明确的诊断。

REF: Rohm Z, Goldman MD, Riley C, Zamvil SS, Pawate S. A 73-Year-Old Woman With Confusion, Visual Field Disturbances, and Edematous White Matter Lesions: From the National Multiple Sclerosis Society Case Conference Proceedings. Neurol Neuroimmunol Neuroinflamm. 2024;11(5):e200300. doi:10.1212/NXI.0000000000200300 PMID: 39141887

Erdheim-Chester Disease Masquerading as CLIPPERS

埃德海姆-切斯特病伪装成快船队

To present 4 patients with Erdheim-Chester disease (ECD) based on clinical, radiologic, histopathologic, and molecular genetic findings who had enhancing brainstem lesions and were initially believed to have chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). ECD is an important CLIPPERS mimic with distinct pathophysiology and targeted treatments. We highlight the need to consider histiocytic disorders among other alternate diagnoses when findings are not classic for CLIPPERS.

根据临床，放射学，组织病理学和分子遗传学发现，介绍4例erdheim-chester病 (ECD) 患者，这些患者的脑干病变增强，最初被认为患有慢性淋巴细胞性炎症，并伴有对类固醇 (CLIPPERS) 有反应的桥脑血管周围增强。ECD是一种重要的CLIPPERS模拟物，具有独特的病理生理学和靶向治疗。当快船的发现不典型时，我们强调需要在其他替代诊断中考虑组织细胞疾病。

REF: Erdheim-Chester Disease Masquerading as CLIPPERS. Neurol Neuroimmunol Neuroinflamm. 2024;11(6):e200317. doi:10.1212/NXI.0000000000200317 PMID: 39213471

Different Complement Activation Patterns Following C5 Cleavage in MOGAD and AQP4-IgG+NMOSD

MOGAD和AQP4-IgG NMOSD中C5裂解后的不同补体激活模式

In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD. These findings may have pathogenetic and therapeutic implications in MOGAD.

在髓磷脂少突胶质细胞糖蛋白IgG相关疾病 (MOGAD) 和aquaporin-4 IgG视神经脊髓炎谱系疾病 (AQP4 NMOSD) 中，自身抗体主要由IgG1组成，补体依赖性细胞毒性是AQP4 NMOSD的主要病理机制。我们旨在评估MOGAD中的CSF补体激活。这些发现可能对MOGAD具有致病和治疗意义。

REF: Kaneko K, Kuroda H, Matsumoto Y, et al. Different Complement Activation Patterns Following C5 Cleavage in MOGAD and AQP4-IgG+NMOSD. Neurol Neuroimmunol Neuroinflamm. 2024;11(5):e200293. doi:10.1212/NXI.0000000000200293 PMID: 39133885

CD19-Directed CAR T-Cells in a Patient With Refractory MOGAD: Clinical and Immunologic Follow-Up for 1 Year

CD19-Directed难治性MOGAD患者的car-t细胞: 临床和免疫学随访1年

In MOG antibody-associated disease (MOGAD), relapse prevention and the treatment approach to refractory symptoms are unknown. We report a patient with refractory MOGAD treated with CD19-directed CAR T-cells. This clinical case shows that CD19-directed CAR T-cell therapy is well-tolerated and is a potential treatment for patients with refractory MOGAD.

在MOG抗体相关疾病 (MOGAD) 中，复发预防和难治性症状的治疗方法尚不清楚。我们报告了一例用CD19-directed CAR T细胞治疗的难治性MOGAD患者。该临床病例表明，CD19-directed car-t细胞疗法耐受性良好，是难治性MOGAD患者的潜在治疗方法。

REF: Cabrera-Maqueda JM, Sepulveda M, García RR, et al. CD19-Directed CAR T-Cells in a Patient With Refractory MOGAD: Clinical and Immunologic Follow-Up for 1 Year. Neurol Neuroimmunol Neuroinflamm. 2024;11(5):e200292. doi:10.1212/NXI.0000000000200292 PMID: 39106426

Opsoclonus-Ataxia Syndrome in a Patient With Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

免疫检查点抑制剂治疗小细胞肺癌患者的视索共济失调综合征

To describe a case of post-immune checkpoint inhibitor (ICI) opsoclonus-myoclonus-ataxia syndrome (OMAS), with complete clinical remission after treatment. The clinical pattern and reversibility bring the present case close to a few patients with paraneoplastic OMAS described before the ICI era. More research is needed to clarify the pathogenesis and outcomes of OMAS in the context of ICI.

描述1例免疫检查点抑制剂 (ICI) 后肌阵挛-共济失调综合征 (OMAS)，治疗后临床完全缓解。临床模式和可逆性使本病例接近ICI时代之前描述的少数副肿瘤性肿瘤患者。需要更多的研究来阐明ICI背景下OMAS的发病机制和结局。

REF: Farina A, Villagrán-García M, Benaiteau M, et al. Opsoclonus-Ataxia Syndrome in a Patient With Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors. Neurol Neuroimmunol Neuroinflamm. 2024;11(5):e200287. doi:10.1212/NXI.0000000000200287 PMID: 39013128

Relapsing-Remitting Immunotherapy Responsive Small-Fiber Neuropathy: Longitudinal Tracking Through 10 Years Including Pregnancies

复发缓解型免疫治疗反应性小纤维神经病: 包括妊娠在内的10年纵向追踪

To expand understanding of the pathogenesis, presentations, and treatment of initially idiopathic small fiber polyneuropathy (SFN). This decade of tracking characterizes a relapsing-remitting course of SFN with initially separated monophasic episodes becoming more confluent, as with multiple sclerosis. This tempo and responsiveness to 5 immunotherapies suggest dysimmune causality. Validated metrics helped define the course and track treatment efficacy, particularly during pregnancy and breastfeeding.

扩大对最初特发性小纤维多发性神经病 (SFN) 的发病机制，表现和治疗的理解。这十年的追踪特征是SFN的复发缓解过程，与多发性硬化症一样，最初分离的单相发作变得更加融合。这种速度和对5种免疫疗法的反应性表明存在免疫障碍的因果关系。经过验证的指标有助于确定疗程并跟踪治疗效果，特别是在怀孕和哺乳期间。

REF: Oaklander AL, Allen J, Dietliker N, Wilder-Smith EP. Relapsing-Remitting Immunotherapy Responsive Small-Fiber Neuropathy: Longitudinal Tracking Through 10 Years Including Pregnancies. Neurol Neuroimmunol Neuroinflamm. 2024;11(5):e200286. doi:10.1212/NXI.0000000000200286 PMID: 39047208

Young-Onset Alzheimer Dementia Due to a Novel Pathogenic Presenilin 1 Variant Initially Misdiagnosed as Autoimmune Encephalitis

由最初被误诊为自身免疫性脑炎的新型致病性早老素1变体引起的年轻阿尔茨海默氏痴呆

Pathogenic variants in presenilin 1 (PSEN1) are related to early-onset Alzheimer disease (AD) and may occur as de novo variants. Because PSEN1 can occur in young patients who lack a family history of neurologic disorders and because these symptoms are also frequent in autoimmune encephalitis (AE), diagnosis may be overlooked. Our aim was to demonstrate the challenge in diagnosing young patients with neurodegenerative diseases that simulate AE.This case demonstrates the importance of considering PSEN1 in young patients with insidious progressive dementia with atypical clinical and neuroimaging features, even in patients without a family history of neurologic disorders.

早老素1 (PSEN1) 的致病变体与早发性阿尔茨海默病 (AD) 有关，并且可能作为从头变体出现。由于PSEN1可能发生在缺乏神经系统疾病家族史的年轻患者中，并且由于这些症状在自身免疫性脑炎 (AE) 中也很常见，因此可能会忽略诊断。我们的目的是证明在诊断患有模拟AE的神经退行性疾病的年轻患者时所面临的挑战。该病例证明了在具有非典型临床和神经影像学特征的隐匿性进行性痴呆的年轻患者中考虑PSEN1的重要性，即使在没有神经系统疾病家族史的患者中也是如此。

REF: Ronchi NR, Castro MA, Coutinho AM, et al. Young-Onset Alzheimer Dementia Due to a Novel Pathogenic Presenilin 1 Variant Initially Misdiagnosed as Autoimmune Encephalitis. Neurol Neuroimmunol Neuroinflamm. 2024;11(5):e200280. doi:10.1212/NXI.0000000000200280 PMID: 39024526

Neurofilament Light Chain Serum Levels Mirror Age and Disability in Secondary Progressive Multiple Sclerosis: A Cross-Sectional Study

继发性进行性多发性硬化症的神经丝轻链血清水平反映了年龄和残疾: 一项横断面研究

To assess neurofilament light chain serum (sNfL) levels in patients with secondary progressive multiple sclerosis (SP-MS). These findings highlight that measurement of sNfL levels represents a useful tool to assess the extent of neuroaxonal damage as a surrogate for clinical progression in patients with SP-MS, when age and disease activity as major confounders are taken into account.

评估继发性进行性多发性硬化症 (sp-ms) 患者血清神经丝轻链 (sNfL) 水平。这些发现突出表明，当将年龄和疾病活动作为主要混杂因素考虑在内时，sNfL水平的测量代表了评估神经轴突损伤程度作为sp-ms患者临床进展的替代的有用工具。

REF: Husseini L, Jung J, Boess N, et al. Neurofilament Light Chain Serum Levels Mirror Age and Disability in Secondary Progressive Multiple Sclerosis: A Cross-Sectional Study. Neurol Neuroimmunol Neuroinflamm. 2024;11(5):e200279. doi:10.1212/NXI.0000000000200279 PMID: 38991171