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"Lupus Myelitis" Revisited: A Retrospective Single-Center Study of Myelitis Associated With Rheumatologic Disease. "狼疮性脊髓炎 "重新审视:风湿病相关骨髓炎的单中心回顾性研究
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-23 DOI: 10.1212/NXI.0000000000200329
Jonathan D Krett, Angeliki G Filippatou, Paula Barreras, Carlos A Pardo, Allan C Gelber, Elias S Sotirchos

Background and objectives: Previous reports of patients with myelitis associated with rheumatologic disease may have had unrecognized aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD). We clinicoradiologically and serologically characterized patients with myelitis associated with rheumatologic disease evaluated in the era of availability of MOG-IgG and more sensitive AQP4-IgG cell-based assays.

Methods: A retrospective cohort (2018-2023) at Johns Hopkins Medicine with diagnoses of myelopathy and rheumatologic comorbidity was identified by electronic medical record (EMR) query. All patients with myelitis unrelated to typical multiple sclerosis (MS) were included and analyzed by chart review.

Results: Of 238 patients identified by EMR query, 197 were excluded (148 not meeting prespecified inclusion criteria, 49 had typical MS), resulting in 41 patients for review. The mean age at myelitis onset was 44 ± 15 years; 39 (95%) were female. Rheumatologic diagnoses included 17 (41.5%) with systemic lupus erythematosus (SLE), 10 (24.3%) Sjögren syndrome (SS), 6 (15%) undifferentiated connective tissue disease (UCTD), 5 (12%) combinations of SLE/SS/UCTD with antiphospholipid antibody syndrome, 1 (2.4%) rheumatoid arthritis, 1 (2.4%) psoriatic arthritis, and 1 (2.4%) Behçet disease. 20 patients (49%) were diagnosed with AQP4-IgG seropositive NMOSD, 3 (7%) with MOGAD, and 18 (44%) had "double-seronegative" myelitis. Of these 18, 3 were diagnosed with AQP4-IgG seronegative NMOSD, 1 neuro-Behçet disease, and 14 other (unclassifiable) myelitis. Excluding 1 patient with neuro-Behçet disease, 18 (90%) of 20 AQP4-IgG seropositive patients had longitudinally extensive cord lesions compared with 5 (29%; p < 0.001) of 17 "double-seronegative" patients and 2 (67%) of 3 with MOGAD. "Double-seronegative" patients more commonly had CSF-restricted oligoclonal bands. Functional outcomes did not differ by diagnosis, and most patients received acute immunotherapy at the time of initial myelitis diagnosis with at least partial recovery over a median follow-up of 38 (interquartile range: 9-74) months.

Discussion: Approximately half of our rheumatologic disease cohort with myelitis unrelated to MS had AQP4-IgG seropositive NMOSD while MOGAD accounted for a small but clinically relevant proportion of patients. Further research is needed to characterize myelitis etiology in patients who are seronegative for both AQP4-IgG and MOG-IgG.

背景和目的:以前报道的与风湿病相关的脊髓炎患者中可能有未被发现的水通道蛋白-4(AQP4)-IgG血清阳性神经脊髓炎视谱系障碍(NMOSD)或髓鞘少突胶质细胞糖蛋白(MOG)-IgG相关疾病(MOGAD)。我们从临床放射学和血清学的角度对与风湿病相关的脊髓炎患者进行了评估,评估是在可以使用MOG-IgG和更灵敏的AQP4-IgG细胞检测的时代进行的:通过电子病历(EMR)查询,确定了约翰霍普金斯医学院诊断为脊髓病和风湿病合并症的回顾性队列(2018-2023 年)。所有与典型多发性硬化症(MS)无关的脊髓炎患者都被纳入其中,并通过病历审查进行分析:在通过电子病历查询确定的 238 名患者中,有 197 人被排除在外(148 人不符合预先确定的纳入标准,49 人患有典型多发性硬化症),最终有 41 名患者接受了复查。脊髓炎发病时的平均年龄为 44 ± 15 岁,其中 39 人(95%)为女性。风湿病诊断包括 17 例(41.5%)系统性红斑狼疮(SLE)、10 例(24.3%)患有斯约格伦综合征(SS),6 人(15%)患有未分化结缔组织病(UCTD),5 人(12%)合并有系统性红斑狼疮/SS/UCTD 和抗磷脂抗体综合征,1 人(2.4%)患有类风湿性关节炎,1 人(2.4%)患有银屑病关节炎,1 人(2.4%)患有白塞病。20名患者(49%)被诊断为AQP4-IgG血清反应阳性的NMOSD,3名患者(7%)被诊断为MOGAD,18名患者(44%)患有 "双酮体阴性 "脊髓炎。在这18人中,3人被诊断为AQP4-IgG血清反应阴性的NMOSD,1人被诊断为神经-贝赫切特病,14人被诊断为其他(无法分类的)脊髓炎。除去1名神经-贝赫切特病患者,20名AQP4-IgG血清反应阳性患者中有18名(90%)有纵向广泛的脊髓病变,而17名 "双克隆阴性 "患者中有5名(29%;p < 0.001)和3名MOGAD患者中有2名(67%)有纵向广泛的脊髓病变。"双克隆阴性 "患者更常出现脑脊液限制性寡克隆带。大多数患者在最初确诊脊髓炎时接受了急性免疫治疗,中位随访时间为38个月(四分位间范围:9-74个月),至少部分康复:讨论:在与多发性硬化症无关的脊髓炎风湿病队列中,约有半数患者的AQP4-IgG血清反应呈NMOSD阳性,而MOGAD患者所占比例虽小,但具有临床意义。对于AQP4-IgG和MOG-IgG血清均阴性的脊髓炎患者,还需要进一步研究其病因。
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引用次数: 0
Missing Full Disclosures. 缺少全面披露。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-30 DOI: 10.1212/NXI.0000000000200342
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引用次数: 0
Pediatric MOG-Ab-Associated Encephalitis: Supporting Early Recognition and Treatment. 小儿 MOG-Ab 相关脑炎:支持早期识别和治疗。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-11 DOI: 10.1212/NXI.0000000000200323
Nee Na Kim, Dimitrios Champsas, Michael Eyre, Omar Abdel-Mannan, Vanessa Lee, Alison Skippen, Manali V Chitre, Rob Forsyth, Cheryl Hemingway, Rachel Kneen, Ming Lim, Dipak Ram, Sithara Ramdas, Evangeline Wassmer, Siobhan West, Sukhvir Wright, Asthik Biswas, Kshitij Mankad, Eoin P Flanagan, Jacqueline Palace, Thomas Rossor, Olga Ciccarelli, Yael Hacohen

Background and objectives: Antibodies to myelin oligodendrocyte glycoprotein (MOG-Ab) have recently been reported in patients with encephalitis who do not fulfill criteria for acute disseminated encephalomyelitis (ADEM). We evaluated a cohort of these children and compared them with children with ADEM.

Methods: This retrospective, multicenter cohort study comprised consecutive patients <18 years of age with MOG-Ab who fulfilled criteria for autoimmune encephalitis. These patients were stratified into (1) children not fulfilling criteria for ADEM (encephalitis phenotype) and (2) children with ADEM. Clinical/paraclinical data were extracted from the electronic records. Comparisons were made using the Mann-Whitney U test and χ2 Fisher exact test for statistical analysis.

Results: From 235 patients with positive MOG-Ab, we identified 33 (14%) with encephalitis and 74 (31%) with ADEM. The most common presenting symptoms in children with encephalitis were headache (88%), seizures (73%), and fever (67%). Infective meningoencephalitis was the initial diagnosis in 67%. CSF pleocytosis was seen in 79%. Initial MRI brain was normal in 8/33 (24%) patients. When abnormal, multifocal cortical changes were seen in 66% and unilateral cortical changes in 18%. Restricted diffusion was demonstrated in 43%. Intra-attack new lesions were seen in 7/13 (54%). When comparing with children with ADEM, children with encephalitis were older (median 8.9 vs 5.7 years, p = 0.005), were more likely to be admitted to intensive care (14/34 vs 4/74, p < 0.0001), were given steroid later (median 16.6 vs 9.6 days, p = 0.04), and were more likely to be diagnosed with epilepsy at last follow-up (6/33 vs 1/74, p = 0.003).

Discussion: MOG-Ab should be tested in all patients with suspected encephalitis even in the context of initially normal brain MRI. Although exclusion of infections should be part of the diagnostic process of any child with encephalitis, in immunocompetent children, when herpes simplex virus CSF PCR and gram stains are negative, these features do not preclude the diagnosis of immune mediated disease and should not delay initiation of first-line immunosuppression (steroids, IVIG, plasma exchange), even while awaiting the antibody results.

背景和目的:最近有报道称,不符合急性播散性脑脊髓炎(ADEM)标准的脑炎患者体内存在髓鞘少突胶质细胞糖蛋白(MOG-Ab)抗体。我们对这些儿童进行了评估,并与患有 ADEM 的儿童进行了比较:这项回顾性多中心队列研究由连续患者组成,采用 U 检验和 χ2 Fisher exact 检验进行统计分析:从 235 例 MOG-Ab 阳性的患者中,我们发现 33 例(14%)患有脑炎,74 例(31%)患有 ADEM。脑炎患儿最常见的症状是头痛(88%)、癫痫发作(73%)和发热(67%)。感染性脑膜脑炎是67%患儿的初步诊断。79%的患者出现脑脊液多细胞现象。8/33(24%)名患者的最初脑部核磁共振成像正常。如果出现异常,66%的患者出现多灶性皮质改变,18%的患者出现单侧皮质改变。43%的患者弥散受限。7/13(54%)的患者在发病时出现新的病变。与ADEM患儿相比,脑炎患儿年龄更大(中位数为8.9岁 vs 5.7岁,p = 0.005),更有可能入住重症监护室(14/34 vs 4/74,p < 0.0001),接受类固醇治疗的时间更晚(中位数为16.6天 vs 9.6天,p = 0.04),最后一次随访时更有可能被诊断为癫痫(6/33 vs 1/74,p = 0.003):讨论:所有疑似脑炎患者都应进行 MOG-Ab 检测,即使最初的脑磁共振成像正常。虽然排除感染应该是所有脑炎患儿诊断过程的一部分,但对于免疫功能正常的患儿,当单纯疱疹病毒CSF PCR和革兰染色阴性时,这些特征并不能排除免疫介导疾病的诊断,即使在等待抗体结果期间,也不应延迟一线免疫抑制(类固醇、IVIG、血浆置换)的启动。
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引用次数: 0
Pharmacokinetics and Pharmacodynamics of Natalizumab 6-Week Dosing vs Continued 4-Week Dosing for Relapsing-Remitting Multiple Sclerosis. 纳他珠单抗治疗复发缓解型多发性硬化症的药代动力学和药效学:6 周用药与持续 4 周用药对比
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-11 DOI: 10.1212/NXI.0000000000200321
John F Foley, Gilles Defer, Lana Zhovtis Ryerson, Jeffrey A Cohen, Douglas L Arnold, Helmut Butzkueven, Gary R Cutter, Gavin Giovannoni, Joep Killestein, Heinz Wiendl, Kexuan Li, Liesel Dsilva, Marie Toukam, Kyle Ferber, Jihee Sohn, Holly Engelman, Tyler Lasky

Background and objectives: Exposure to natalizumab, an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS), is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Compared with every-4-week (Q4W) dosing, extended-interval dosing of natalizumab is associated with decreased risk of PML. Clinical efficacy was maintained in the majority of patients switched to every-6-week (Q6W) dosing in the phase 3b NOVA clinical trial. In this article, we report pharmacokinetics (PK) and pharmacodynamics (PD) of Q6W vs Q4W dosing in NOVA.

Methods: In NOVA study Part 1, participants with RRMS (aged 18-60 years) and Expanded Disability Status Scale score <5.5, who were stable on IV natalizumab Q4W dosing for ≥12 months, were randomized to continue IV Q4W dosing or switched to IV Q6W dosing of natalizumab and followed for 72 weeks. Exploratory outcomes were measurements of trough serum natalizumab concentration, α4-integrin saturation, and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration. A mixed model of repeated measures was used to estimate mean treatment differences between groups. Patient-level PK and PD data were examined in those with relapse or radiologic disease activity.

Results: In NOVA, 486 (Q6W, n = 245; Q4W, n = 241) and 487 (Q6W, n = 246; Q4W, n = 241) participants were included in the PK and PD populations, respectively. Mean trough natalizumab concentrations ranged from 10 to 21 μg/mL (Q6W) and 33-38 μg/mL (Q4W), and mean α4-integrin saturation remained above 65.5% (Q6W) and above 77.9% (Q4W). In the Q6W group, mean sVCAM-1 levels increased 23.6% by week 24 and remained elevated throughout the study, while mean sVCAM-1 levels remained generally stable in the Q4W group. Most participants with T2 lesion activity or relapse activity, in either treatment arm, maintained trough natalizumab levels >10 μg/mL and trough α4-integrin saturation >50%.

Discussion: Compared with Q4W dosing, Q6W dosing was associated with a 60%-70% decrease in mean trough natalizumab levels and a 9%-16% decrease in mean α4-integrin saturation. At the patient level, neither natalizumab concentration nor α4-integrin saturation was consistently predictive of lesion or relapse activity, suggesting that trough natalizumab and α4-integrin saturation measurements should be interpreted with caution in clinical practice.

Trial registration information: ClinicalTrials.gov, NCT03689972; EudraCT, 2018-002145-11. Submitted 2018-09-27. First patient enrolled: 2018-12-26. https://clinicaltrials.gov/study/NCT03689972.

背景和目的:纳他珠单抗是治疗复发缓解型多发性硬化症(RRMS)的一种有效药物,它的暴露与进行性多灶性白质脑病(PML)风险的增加有关。与每四周一次(Q4W)给药相比,纳他珠单抗的延长间隔给药可降低PML风险。在3b期NOVA临床试验中,大多数改用每6周(Q6W)给药的患者都保持了临床疗效。本文报告了 NOVA 中 Q6W 与 Q4W 给药的药代动力学(PK)和药效学(PD):在 NOVA 研究的第一部分中,参与者均为 RRMS 患者(18-60 岁),且残疾状况扩展量表评分为结果:在NOVA研究中,PK组和PD组分别有486名(Q6W,n = 245;Q4W,n = 241)和487名(Q6W,n = 246;Q4W,n = 241)参与者。纳妥珠单抗的平均谷浓度范围为10-21 μg/mL(Q6W)和33-38 μg/mL(Q4W),α4-整合素的平均饱和度保持在65.5%以上(Q6W)和77.9%以上(Q4W)。在 Q6W 组中,sVCAM-1 的平均水平在第 24 周时增加了 23.6%,并在整个研究期间保持升高,而在 Q4W 组中,sVCAM-1 的平均水平基本保持稳定。在任一治疗组中,大多数有T2病变活动或复发活动的参与者都保持了纳他珠单抗谷值>10 μg/mL和α4-整合素谷值饱和度>50%的水平:讨论:与Q4W给药相比,Q6W给药与纳他珠单抗平均谷值降低60%-70%和α4-整合素平均饱和度降低9%-16%有关。在患者水平上,纳他珠单抗浓度和α4-整合素饱和度都不能持续预测病变或复发活动,这表明在临床实践中应谨慎解释纳他珠单抗和α4-整合素饱和度谷值:ClinicalTrials.gov,NCT03689972;EudraCT,2018-002145-11。提交时间:2018-09-27。首例患者入组:2018-12-26。https://clinicaltrials.gov/study/NCT03689972。
{"title":"Pharmacokinetics and Pharmacodynamics of Natalizumab 6-Week Dosing vs Continued 4-Week Dosing for Relapsing-Remitting Multiple Sclerosis.","authors":"John F Foley, Gilles Defer, Lana Zhovtis Ryerson, Jeffrey A Cohen, Douglas L Arnold, Helmut Butzkueven, Gary R Cutter, Gavin Giovannoni, Joep Killestein, Heinz Wiendl, Kexuan Li, Liesel Dsilva, Marie Toukam, Kyle Ferber, Jihee Sohn, Holly Engelman, Tyler Lasky","doi":"10.1212/NXI.0000000000200321","DOIUrl":"10.1212/NXI.0000000000200321","url":null,"abstract":"<p><strong>Background and objectives: </strong>Exposure to natalizumab, an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS), is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Compared with every-4-week (Q4W) dosing, extended-interval dosing of natalizumab is associated with decreased risk of PML. Clinical efficacy was maintained in the majority of patients switched to every-6-week (Q6W) dosing in the phase 3b NOVA clinical trial. In this article, we report pharmacokinetics (PK) and pharmacodynamics (PD) of Q6W vs Q4W dosing in NOVA.</p><p><strong>Methods: </strong>In NOVA study Part 1, participants with RRMS (aged 18-60 years) and Expanded Disability Status Scale score <5.5, who were stable on IV natalizumab Q4W dosing for ≥12 months, were randomized to continue IV Q4W dosing or switched to IV Q6W dosing of natalizumab and followed for 72 weeks. Exploratory outcomes were measurements of trough serum natalizumab concentration, α4-integrin saturation, and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration. A mixed model of repeated measures was used to estimate mean treatment differences between groups. Patient-level PK and PD data were examined in those with relapse or radiologic disease activity.</p><p><strong>Results: </strong>In NOVA, 486 (Q6W, n = 245; Q4W, n = 241) and 487 (Q6W, n = 246; Q4W, n = 241) participants were included in the PK and PD populations, respectively. Mean trough natalizumab concentrations ranged from 10 to 21 μg/mL (Q6W) and 33-38 μg/mL (Q4W), and mean α4-integrin saturation remained above 65.5% (Q6W) and above 77.9% (Q4W). In the Q6W group, mean sVCAM-1 levels increased 23.6% by week 24 and remained elevated throughout the study, while mean sVCAM-1 levels remained generally stable in the Q4W group. Most participants with T2 lesion activity or relapse activity, in either treatment arm, maintained trough natalizumab levels >10 μg/mL and trough α4-integrin saturation >50%.</p><p><strong>Discussion: </strong>Compared with Q4W dosing, Q6W dosing was associated with a 60%-70% decrease in mean trough natalizumab levels and a 9%-16% decrease in mean α4-integrin saturation. At the patient level, neither natalizumab concentration nor α4-integrin saturation was consistently predictive of lesion or relapse activity, suggesting that trough natalizumab and α4-integrin saturation measurements should be interpreted with caution in clinical practice.</p><p><strong>Trial registration information: </strong>ClinicalTrials.gov, NCT03689972; EudraCT, 2018-002145-11. Submitted 2018-09-27. First patient enrolled: 2018-12-26. https://clinicaltrials.gov/study/NCT03689972.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive Analysis of Paraneoplastic Neurologic Syndrome and PNS-CARE Diagnostic Criteria in Clinical Practice. 全面分析副肿瘤性神经综合征和 PNS-CARE 诊断标准在临床实践中的应用。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-25 DOI: 10.1212/NXI.0000000000200316
Hannah Zhao-Fleming, Mohamed Rezk, Shailee Shah, Pranjal Gupta, Anastasia Zekeridou, Eoin P Flanagan, Sean J Pittock, Andrew McKeon, Divyanshu Dubey

Background and objectives: Paraneoplastic neurologic syndrome (PNS) diagnostic criteria were first proposed in 2004 and updated in 2021. The PNS-CARE score, derived from the updated criteria, is a composite model for assigning likelihood for patients with suspected PNS. In this study, we evaluated the utility and applicability of the 2021 PNS-CARE score and present our PNS cohort.

Methods: This is a retrospective study. We identified Mayo Clinic patients suspected to have PNS (1/2005-12/2020) and collected relevant information including demographics, PNS presentation, and clinical outcomes. Inclusion criteria were the following: (1) patients with a syndrome consistent with PNS and (2) patients with sufficient information available in charts. Exclusion criteria were the following: (1) evaluation only before 2005, (2) patients not evaluated by neurology, (3) presentation after immune checkpoint inhibitors, and (4) syndromes not included in 2021 criteria. All patients were evaluated for the 2021 and 2004 PNS criteria.

Results: We identified 484 patients suspected to have PNS at initial presentation, of whom 212 (44%) were considered to have PNS after completion of evaluation. Among these 212 patients, the most common autoantibodies were PCA1 (Yo)-IgG (17%), KLHL11-IgG (16%), and CRMP5-IgG (14%) and the most common phenotypes were rapidly progressive cerebellar syndrome (29%), brainstem encephalitis (14%), and limbic encephalitis (8%). The 2021 PNS criteria definite/probable categorization (PNS-CARE score ≥ 6) had a sensitivity and specificity of 93% and 100%, respectively, while the 2004 PNS criteria definite categorization had a sensitivity and specificity of 67% and 99%, respectively. We found 15 patients with a PNS-CARE score ≤5 who likely had PNS on our review. The most common presentation among these patients was KLHL11-IgG brainstem encephalitis (7/15, 47%) with likely burned-out testicular tumor.

Discussion: Our study validates the PNS-CARE score. A clearer understanding of typical PNS presentation and common underlying malignancies and autoantibodies can aid in earlier and more accurate diagnosis, which is crucial for downstream clinical decisions. Some patients with an intermediate-risk phenotype do not meet probable/definite criteria despite the presence of high-risk antibodies and/or underlying malignancy.

背景和目的:副肿瘤性神经综合征(PNS)诊断标准于 2004 年首次提出,并于 2021 年更新。PNS-CARE评分源于更新后的标准,是为疑似PNS患者分配可能性的综合模型。在本研究中,我们评估了 2021 年 PNS-CARE 评分的实用性和适用性,并介绍了我们的 PNS 队列:这是一项回顾性研究。我们确定了梅奥诊所的疑似 PNS 患者(1/2005-12/2020),并收集了相关信息,包括人口统计学、PNS 表现和临床结果。纳入标准如下:(1) 具有与 PNS 一致的综合征的患者;(2) 病历中有足够信息的患者。排除标准如下:(1)仅在 2005 年前进行过评估的患者;(2)未经神经内科评估的患者;(3)使用免疫检查点抑制剂后发病的患者;(4)未纳入 2021 年标准的综合征患者。所有患者均根据 2021 年和 2004 年 PNS 标准进行了评估:我们确定了 484 名在初次就诊时被怀疑患有 PNS 的患者,其中 212 人(44%)在完成评估后被认为患有 PNS。在这212名患者中,最常见的自身抗体是PCA1 (Yo)-IgG(17%)、KLHL11-IgG(16%)和CRMP5-IgG(14%),最常见的表型是快速进展性小脑综合征(29%)、脑干脑炎(14%)和肢端脑炎(8%)。2021 年 PNS 标准明确/可能分类(PNS-CARE 评分≥ 6 分)的敏感性和特异性分别为 93% 和 100%,而 2004 年 PNS 标准明确分类的敏感性和特异性分别为 67% 和 99%。我们在复查中发现,15 名 PNS-CARE 评分≤5 分的患者可能患有 PNS。这些患者中最常见的表现是 KLHL11-IgG 脑干脑炎(7/15,47%),并可能伴有灼伤性睾丸肿瘤:讨论:我们的研究验证了 PNS-CARE 评分。更清楚地了解典型的 PNS 表现以及常见的潜在恶性肿瘤和自身抗体有助于更早、更准确地做出诊断,这对下游临床决策至关重要。一些中危表型患者尽管存在高危抗体和/或潜在恶性肿瘤,但并不符合可能/无限期标准。
{"title":"Comprehensive Analysis of Paraneoplastic Neurologic Syndrome and PNS-CARE Diagnostic Criteria in Clinical Practice.","authors":"Hannah Zhao-Fleming, Mohamed Rezk, Shailee Shah, Pranjal Gupta, Anastasia Zekeridou, Eoin P Flanagan, Sean J Pittock, Andrew McKeon, Divyanshu Dubey","doi":"10.1212/NXI.0000000000200316","DOIUrl":"10.1212/NXI.0000000000200316","url":null,"abstract":"<p><strong>Background and objectives: </strong>Paraneoplastic neurologic syndrome (PNS) diagnostic criteria were first proposed in 2004 and updated in 2021. The PNS-CARE score, derived from the updated criteria, is a composite model for assigning likelihood for patients with suspected PNS. In this study, we evaluated the utility and applicability of the 2021 PNS-CARE score and present our PNS cohort.</p><p><strong>Methods: </strong>This is a retrospective study. We identified Mayo Clinic patients suspected to have PNS (1/2005-12/2020) and collected relevant information including demographics, PNS presentation, and clinical outcomes. Inclusion criteria were the following: (1) patients with a syndrome consistent with PNS and (2) patients with sufficient information available in charts. Exclusion criteria were the following: (1) evaluation only before 2005, (2) patients not evaluated by neurology, (3) presentation after immune checkpoint inhibitors, and (4) syndromes not included in 2021 criteria. All patients were evaluated for the 2021 and 2004 PNS criteria.</p><p><strong>Results: </strong>We identified 484 patients suspected to have PNS at initial presentation, of whom 212 (44%) were considered to have PNS after completion of evaluation. Among these 212 patients, the most common autoantibodies were PCA1 (Yo)-IgG (17%), KLHL11-IgG (16%), and CRMP5-IgG (14%) and the most common phenotypes were rapidly progressive cerebellar syndrome (29%), brainstem encephalitis (14%), and limbic encephalitis (8%). The 2021 PNS criteria definite/probable categorization (PNS-CARE score ≥ 6) had a sensitivity and specificity of 93% and 100%, respectively, while the 2004 PNS criteria definite categorization had a sensitivity and specificity of 67% and 99%, respectively. We found 15 patients with a PNS-CARE score ≤5 who likely had PNS on our review. The most common presentation among these patients was KLHL11-IgG brainstem encephalitis (7/15, 47%) with likely burned-out testicular tumor.</p><p><strong>Discussion: </strong>Our study validates the PNS-CARE score. A clearer understanding of typical PNS presentation and common underlying malignancies and autoantibodies can aid in earlier and more accurate diagnosis, which is crucial for downstream clinical decisions. Some patients with an intermediate-risk phenotype do not meet probable/definite criteria despite the presence of high-risk antibodies and/or underlying malignancy.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cognitive Impairment, Associated Clinical Factors, and MR Volumetric Measures in Myelin Oligodendrocyte Glycoprotein-IgG-Associated Disease. 髓鞘寡突胶质细胞糖蛋白-IgG相关疾病的认知障碍、相关临床因素和磁共振容积测量。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-11 DOI: 10.1212/NXI.0000000000200325
Ann-Kathrin Kogel, Theodoros Ladopoulos, Carolin Schwake, Ingo Kleiter, Bianca Teegen, Nadine Siems, Christian Prehn, Solveig Lichtenberg, Marius Ringelstein, Orhan Aktas, Refik Pul, Britta Krieger, Carsten Lukas, Iris-Katharina Penner, Ralf Gold, Ruth Schneider, Ilya Ayzenberg

Background and objectives: Cognitive impairment is a common and challenging symptom in multiple sclerosis and neuromyelitis optica spectrum disease; however, data in myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) remain scarce. In this cross-sectional study, we investigated the frequency of cognitive impairment, associated clinical factors, and MRI volumetric measures in MOGAD.

Methods: Participants were investigated in a single center by certified psychologists and underwent a standardized 3-T-MRI protocol. MRI data were processed with FreeSurfer for gray and white matter volume estimation, presented as a fraction of total intracranial volume. Sera screening for antineural antibodies has been conducted using cell-based assays. The following clinical factors were included in the multivariate logistic regression analysis: sex, age, overall number of previous relapses, and specifically the history of acute disseminated encephalomyelitis (ADEM)/ADEM-like episodes and other brain relapses.

Results: Thirty-two patients with MOGAD (19 female, median age 29.4 years) after a median of 2 relapses with a median EDSS of 1.0 were recruited. Seven patients (21.9%) demonstrated cognitive impairment with the most prevalent deficits in mental flexibility (16.7%), attention (11.1%-14.8%), and verbal working memory (10.3%). 72.4% suffered from fatigue and 42.9% from signs of depression, moderate to severe in 28.6%. The overall number of previous relapses (odds ratio [OR] 1.789, 95% CI 1.041-3.074) and specifically ADEM/ADEM-like episodes (OR 16.929, 95% CI 1.228-233.427) were the only clinical factors associated with cognitive impairment in a multivariate logistic regression model. Screening for antineuronal antibodies remained negative. Cerebral white matter (WM) (0.300 vs 0.317, p = 0.003) and deep gray matter (DGM) (0.036 vs 0.038, p = 0.002) volumes were reduced in patients with MOGAD compared with healthy controls (n = 32). Both cognitive impairment (0.031 vs 0.036, p = 0.003) and history of ADEM/ADEM-like episodes (0.032 vs 0.036, p = 0.006) were associated with reduced DGM volume compared with unaffected patients with MOGAD.

Discussion: Despite a low overall disability, every 5th patient with MOGAD experiences cognitive impairment. Cognitive impairment is associated with a higher number of relapses and particularly ADEM/ADEM-like attacks. Although both WM and DGM atrophies are apparent in MOGAD, the latter only seems to have an association with cognitive impairment.

背景和目的:认知障碍是多发性硬化症和神经性脊髓炎视网膜频谱疾病中常见且具有挑战性的症状;然而,有关髓鞘少突胶质细胞糖蛋白-IgG相关疾病(MOGAD)的数据仍然很少。在这项横断面研究中,我们调查了MOGAD患者出现认知障碍的频率、相关临床因素和磁共振成像容积测量:参与者在一个中心接受由认证心理学家进行的调查,并接受标准化的 3-T-MRI 方案。用FreeSurfer处理磁共振成像数据,估算灰质和白质体积,并以颅内总体积的百分比表示。抗神经抗体的血清筛查采用细胞检测法进行。多变量逻辑回归分析包括以下临床因素:性别、年龄、既往复发总次数,特别是急性播散性脑脊髓炎(ADEM)/ADEM样发作史和其他脑部复发史:共招募了 32 名 MOGAD 患者(19 名女性,中位年龄为 29.4 岁),他们的中位复发次数为 2 次,中位 EDSS 为 1.0。7名患者(21.9%)表现出认知障碍,最普遍的障碍表现为智力灵活性(16.7%)、注意力(11.1%-14.8%)和言语工作记忆(10.3%)。72.4%的患者有疲劳感,42.9%的患者有抑郁迹象,28.6%的患者有中度至重度抑郁。在多变量逻辑回归模型中,既往复发的总次数(比值比 [OR] 1.789,95% CI 1.041-3.074)和具体的 ADEM/ADEM-类发作(比值比 16.929,95% CI 1.228-233.427)是与认知障碍相关的唯一临床因素。抗神经元抗体筛查结果仍为阴性。与健康对照组(32 人)相比,MOGAD 患者的脑白质(WM)(0.300 vs 0.317,p = 0.003)和深灰质(DGM)(0.036 vs 0.038,p = 0.002)体积缩小。与未受影响的 MOGAD 患者相比,认知障碍(0.031 vs 0.036,p = 0.003)和 ADEM/ADEM 类发作史(0.032 vs 0.036,p = 0.006)均与 DGM 体积减少有关:讨论:尽管总体残疾程度较低,但每五名 MOGAD 患者中就有一人出现认知障碍。讨论:尽管 MOGAD 患者的总体残疾程度较低,但每五名患者中就有一人出现认知障碍。认知障碍与较高的复发次数,尤其是 ADEM/ADEM 类发作有关。尽管MOGAD患者的WM和DGM都明显萎缩,但后者似乎只与认知障碍有关。
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引用次数: 0
Immunologic Profiling of CSF in Subarachnoid Neurocysticercosis Reveals Specific Interleukin-10-Producing Cell Populations During Treatment. 蛛网膜下腔神经囊虫病脑脊液免疫学分析揭示了治疗过程中白细胞介素-10的特异性分泌细胞群
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-01 Epub Date: 2024-10-30 DOI: 10.1212/NXI.0000000000200320
Nina L Tang, Paul Schaughency, Pedro Gazzinelli-Guimaraes, Justin Lack, Lauren Thumm, Emily Miltenberger, Theodore E Nash, Thomas B Nutman, Elise M O'Connell

Background and objectives: Subarachnoid neurocysticercosis (SANCC) is the most severe form of Taenia solium CNS infection and accounts for the majority of neurocysticercosis-associated mortality. Inflammation is important in the treatment of SANCC because overactivity can lead to serious complications, but excessive suppression may be counterproductive toward parasite eradication. A relative abundance of CSF IL-10 to IL-12 has been associated with increased treatment duration for patients with SANCC, suggesting that IL-10 plays an important role in this disease process. To better understand SANCC immunology and the major sources of IL-10 during anthelmintic treatment, we took an unbiased and comprehensive approach to phenotype the immune cell populations in the CSF and peripheral blood of patients with SANCC.

Methods: Eight samples of CSF cells collected from 5 patients with SANCC during treatment were evaluated using single-cell RNA sequencing. Matched CSF and peripheral blood mononuclear cells from 4 patients were assessed using flow cytometry. Staining for extracellular and intracellular markers allowed for the characterization of IL-10-producing T cells.

Results: The CSF during SANCC contains a diversity of immune cell populations including multiple myeloid and lymphoid populations. Although there were changes in the composition of CSF cells during treatment, the largest population at both early and late time points was CD4+ T cells. Within this population, we identified 3 sources of IL-10 unique to SANCC CSF compared with controls: natural regulatory T cells (nTregs), induced regulatory T cells (iTregs), and Th17 cells. The abundance and phenotype of these IL-10-producing populations differed between CSF and blood in patients with SANCC, but iTregs were the single most productive population in the CSF. During treatment, these IL-10 producers persisted in consistent proportions despite decreases in parasite antigen over time.

Discussion: This profile of immune cell populations in the CSF provides a comprehensive blueprint of the local and systemic immunology associated with SANCC. The identification of IL-10-producing cells in the CSF and peripheral blood deepens our understanding of the immunosuppressive phenotype that deters SANCC treatment success. Finally, the discovery that these IL-10 producers persist throughout treatment highlights the endurance of these populations in the CNS.

背景和目的:蛛网膜下腔神经囊尾蚴病(SANCC)是中枢神经系统感染中最严重的一种,占神经囊尾蚴病相关死亡率的大多数。炎症在 SANCC 的治疗中非常重要,因为过度活跃会导致严重的并发症,但过度抑制可能会对寄生虫的根除产生反作用。CSF IL-10 相对于 IL-12 的丰度与 SANCC 患者治疗时间的延长有关,这表明 IL-10 在这一疾病过程中发挥着重要作用。为了更好地了解 SANCC 免疫学以及抗蠕虫药物治疗过程中 IL-10 的主要来源,我们采用了一种无偏见的综合方法,对 SANCC 患者 CSF 和外周血中的免疫细胞群进行了表型分析:我们采用单细胞 RNA 测序法对从 5 名 SANCC 患者治疗期间采集的 8 份 CSF 细胞样本进行了评估。使用流式细胞术评估了 4 名患者的匹配 CSF 和外周血单核细胞。通过对细胞外和细胞内标记物进行染色,可以确定产生IL-10的T细胞的特征:结果:SANCC 期间的 CSF 含有多种免疫细胞群,包括多种髓系和淋巴细胞群。虽然在治疗过程中 CSF 细胞的组成发生了变化,但在早期和晚期时间点,CD4+ T 细胞是最大的细胞群。与对照组相比,我们在这一群体中发现了 SANCC CSF 中特有的三种 IL-10 来源:天然调节性 T 细胞(nTregs)、诱导调节性 T 细胞(iTregs)和 Th17 细胞。SANCC患者CSF和血液中产生IL-10的这些细胞群的丰度和表型各不相同,但iTregs是CSF中产生IL-10最多的一个细胞群。在治疗过程中,尽管寄生虫抗原会随着时间的推移而减少,但这些IL-10产生者的比例始终保持不变:讨论:CSF 中免疫细胞群的这一特征提供了与 SANCC 相关的局部和全身免疫学的全面蓝图。CSF 和外周血中分泌 IL-10 的细胞的鉴定加深了我们对阻碍 SANCC 治疗成功的免疫抑制表型的理解。最后,我们还发现这些IL-10产生细胞在整个治疗过程中都会持续存在,这突显了这些细胞群在中枢神经系统中的持久性。
{"title":"Immunologic Profiling of CSF in Subarachnoid Neurocysticercosis Reveals Specific Interleukin-10-Producing Cell Populations During Treatment.","authors":"Nina L Tang, Paul Schaughency, Pedro Gazzinelli-Guimaraes, Justin Lack, Lauren Thumm, Emily Miltenberger, Theodore E Nash, Thomas B Nutman, Elise M O'Connell","doi":"10.1212/NXI.0000000000200320","DOIUrl":"10.1212/NXI.0000000000200320","url":null,"abstract":"<p><strong>Background and objectives: </strong>Subarachnoid neurocysticercosis (SANCC) is the most severe form of <i>Taenia solium</i> CNS infection and accounts for the majority of neurocysticercosis-associated mortality. Inflammation is important in the treatment of SANCC because overactivity can lead to serious complications, but excessive suppression may be counterproductive toward parasite eradication. A relative abundance of CSF IL-10 to IL-12 has been associated with increased treatment duration for patients with SANCC, suggesting that IL-10 plays an important role in this disease process. To better understand SANCC immunology and the major sources of IL-10 during anthelmintic treatment, we took an unbiased and comprehensive approach to phenotype the immune cell populations in the CSF and peripheral blood of patients with SANCC.</p><p><strong>Methods: </strong>Eight samples of CSF cells collected from 5 patients with SANCC during treatment were evaluated using single-cell RNA sequencing. Matched CSF and peripheral blood mononuclear cells from 4 patients were assessed using flow cytometry. Staining for extracellular and intracellular markers allowed for the characterization of IL-10-producing T cells.</p><p><strong>Results: </strong>The CSF during SANCC contains a diversity of immune cell populations including multiple myeloid and lymphoid populations. Although there were changes in the composition of CSF cells during treatment, the largest population at both early and late time points was CD4<sup>+</sup> T cells. Within this population, we identified 3 sources of IL-10 unique to SANCC CSF compared with controls: natural regulatory T cells (nTregs), induced regulatory T cells (iTregs), and Th17 cells. The abundance and phenotype of these IL-10-producing populations differed between CSF and blood in patients with SANCC, but iTregs were the single most productive population in the CSF. During treatment, these IL-10 producers persisted in consistent proportions despite decreases in parasite antigen over time.</p><p><strong>Discussion: </strong>This profile of immune cell populations in the CSF provides a comprehensive blueprint of the local and systemic immunology associated with SANCC. The identification of IL-10-producing cells in the CSF and peripheral blood deepens our understanding of the immunosuppressive phenotype that deters SANCC treatment success. Finally, the discovery that these IL-10 producers persist throughout treatment highlights the endurance of these populations in the CNS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A 79-Year-Old Woman With Worsening Headaches and Pachymeningeal Enhancement: A Case Report From the National Multiple Sclerosis Society Case Conference Proceedings. 一位 79 岁的妇女头痛加剧并伴有门脉增强:全国多发性硬化症协会病例会议论文集中的病例报告。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-27 DOI: 10.1212/NXI.0000000000200308
Manali S Sheth, David E Hale, Justin C Mcarthur, Scott S Zamvil, Myla D Goldman, Claire Riley, Tanuja Chitnis

A 79-year-old woman presented with subacutely worsening headaches and right arm weakness. MRI showed diffuse pachymeningeal enhancement. Serologic workup revealed elevated erythrocyte sedimentation rate and C-reactive protein. CSF demonstrated elevated opening pressure, a lymphocytic pleocytosis, and elevated protein. We discuss our differential diagnosis and distinguish between 2 overlapping clinical entities.

一名 79 岁的妇女因亚急性头痛和右臂无力而就诊。核磁共振成像显示弥漫性脑膜增强。血清学检查显示红细胞沉降率和 C 反应蛋白升高。脑脊液显示开口压升高、淋巴细胞增多和蛋白升高。我们讨论了鉴别诊断,并区分了两种重叠的临床实体。
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引用次数: 0
Hemimacular Thinning Due to Lesions in the Lateral Geniculate Nucleus in 2 Patients With Neuroinflammatory Diseases. 两名神经炎患者因侧膝曲核病变导致的眼球变薄
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-14 DOI: 10.1212/NXI.0000000000200297
Kean Schoenholzer, Shaumiya Sellathurai, Federico Burguet Villena, Athina Papadopoulou
{"title":"Hemimacular Thinning Due to Lesions in the Lateral Geniculate Nucleus in 2 Patients With Neuroinflammatory Diseases.","authors":"Kean Schoenholzer, Shaumiya Sellathurai, Federico Burguet Villena, Athina Papadopoulou","doi":"10.1212/NXI.0000000000200297","DOIUrl":"10.1212/NXI.0000000000200297","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Progressive Encephalomyelitis With Rigidity and Myoclonus With Glycine Receptor and GAD65 Antibodies: Case Report and Potential Mechanisms. 伴有甘氨酸受体和 GAD65 抗体的进行性脑脊髓炎伴僵直和肌阵挛:病例报告与潜在机制
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-30 DOI: 10.1212/NXI.0000000000200298
Michael Winklehner, Jonathan Wickel, Ellen Gelpi, Dirk Brämer, Vera Rauschenberger, Albrecht Günther, Jan Bauer, Anika Simonovska Serra, Philipp Jauk, Carmen Villmann, Romana Höftberger, Christian Geis

Objectives: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder that can be associated with antibodies against surface antigens (glycine receptor (GlyR), dipeptidyl-peptidase-like-protein-6) and intracellular antigens (glutamate decarboxylase (GAD65), amphiphysin).

Methods: We report clinico-pathologic findings of a PERM patient with coexisting GlyR and GAD65 antibodies.

Results: A 75-year-old man presented with myoclonus and pain of the legs, subsequently developed severe motor symptoms, hyperekplexia, a pronounced startle reflex, hallucinations, dysautonomia, and died 10 months after onset despite extensive immunotherapy, symptomatic treatment, and continuous intensive care support. Immunotherapy comprised corticosteroids, IVIG, plasmapheresis, immunoadsorption, cyclophosphamide, and bortezomib. Intensive care treatment and permanent isoflurane sedation was required for more than 20 weeks. CNS tissue revealed neuronal loss, astrogliosis and microgliosis, representing a pallido-nigro-dentato-bulbar-spinal degeneration pattern, specifically along GlyR and GAD expression sites. Neurons showed pSTAT1, MHC class I, and GRP78 upregulation. Inflammation was moderate and characterized by CD8+ T cells and single CD20+/CD79a+ B/plasma cells. Focal tau-positive thread-like deposits were detected in gliotic brainstem areas. In the spinal cord, GlyR, glycine transporter-2, and GAD67 expression were strongly reduced.

Discussion: A possible potentiating effect of pathogenic GlyR antibodies together with T cells directed against neurons may have led to the severe and progressive clinical course.

研究目的进行性脑脊髓炎伴僵直和肌阵挛(PERM)是一种严重的僵直性脊髓炎谱系障碍,可能与针对表面抗原(甘氨酸受体(GlyR)、二肽基肽酶样蛋白-6)和细胞内抗原(谷氨酸脱羧酶(GAD65)、两性蛋白)的抗体有关:我们报告了一名同时存在 GlyR 和 GAD65 抗体的 PERM 患者的临床病理结果:一名 75 岁的男性患者出现肌阵挛和腿部疼痛,随后出现严重的运动症状、过度震颤、明显的惊跳反射、幻觉、自主神经功能障碍,尽管接受了广泛的免疫治疗、对症治疗和持续的重症监护支持,患者仍在发病 10 个月后死亡。免疫治疗包括皮质类固醇、静脉注射免疫球蛋白、血浆置换术、免疫吸附、环磷酰胺和硼替佐米。患者需要接受超过20周的重症监护治疗和长期异氟醚镇静。中枢神经系统组织显示神经元缺失、星形胶质细胞增生和小胶质细胞增生,表现为苍白球-尼格罗-齿状突起-横纹肌-脊髓变性模式,特别是沿GlyR和GAD表达位点。神经元显示 pSTAT1、MHC I 类和 GRP78 上调。炎症为中度,以 CD8+ T 细胞和单个 CD20+/CD79a+ B/浆细胞为特征。在脑干胶质区域检测到灶性 tau 阳性线状沉积。在脊髓中,GlyR、甘氨酸转运体-2和GAD67的表达量明显减少:讨论:致病性 GlyR 抗体和针对神经元的 T 细胞可能产生了潜在的增强效应,从而导致了严重的进行性临床病程。
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引用次数: 0
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Neurology® Neuroimmunology & Neuroinflammation
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