视神经脊髓炎患者血清神经丝重链SMI-35临床意义初探

目的探讨视神经脊髓炎(NMO)患者血液神经丝重链(NfH)的水平及其临床意义。方法选取27例NMO患者、20例多发性硬化(MS)患者以及健康志愿者26名,采用ELISA法检测各组血清NfHSMI-35水平及NMO患者血清水通道蛋白抗体(AQP4-IgG)水平,观察NfH在NMO、MS和健康人群间以及在NMO患者AQP4-IgG阳性和阴性组间的差异,同时分析NMO患者NfH水平同NMO受累脊髓节段和临床神经功能缺损程度的相关性。结果NMO组、MS组和健康对照组血清NfHSMI-35水平分别为(0.100±0.024)、(0.082±0.012)和(0.064±0.021)ng/mL,NMO组和MS组血清NfHSMI-35水平均高于健康对照组(P0.05),且NMO组NfHSMI-35水平高于MS组(P0.05);NMO患者AQP4-IgG阳性和阴性者间NfHSMI-35水平比较无统计学差异〔(0.106±0.029)ng/mνs.(0.091±0.013)ng/mL,P0.05〕;NMO组NfHSMI-35水平与脊髓受累节段长度呈正相关(r=0.556,P0.01),与临床扩展致残量表评分(EDSS)无相关性(r=0.214,P0.05)。结论 NMO患者外周血NfHSMI-35明显升高,有可能成为NMO的生物标志物,并有可能成为与MS相鉴别的临床监测指标,但仍需要进一步观察和研究。     

Immunogenetics of autoimmune thyroid diseases: A comprehensive review

Both environmental and genetic triggers factor into the etiology of autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT). Although the exact pathogenesis and causative interaction between environment and genes are unknown, GD and HT share similar immune-mediated mechanisms of disease. They both are characterized by the production of thyroid autoantibodies and by thyroidal lymphocytic infiltration, despite being clinically distinct entities with thyrotoxicosis in GD and hypothyroidism in HT. Family and population studies confirm the strong genetic influence and inheritability in the development of AITD. AITD susceptibility genes can be categorized as either thyroid specific (Tg, TSHR) or immune-modulating (FOXP3, CD25, CD40, CTLA-4, HLA), with HLA-DR3 carrying the highest risk. Of the AITD susceptibility genes, FOXP3 and CD25 play critical roles in the establishment of peripheral tolerance while CD40, CTLA-4, and the HLA genes are pivotal for T lymphocyte activation and antigen presentation. Polymorphisms in these immune-modulating genes, in particular, significantly contribute to the predisposition for GD, HT and, unsurprisingly, other autoimmune diseases. Emerging evidence suggests that single nucleotide polymorphisms (SNPs) in the immunoregulatory genes may functionally hinder the proper development of central and peripheral tolerance and alter T cell interactions with antigen presenting cells (APCs) in the immunological synapse. Thus, susceptibility genes for AITD contribute directly to the key mechanism underlying the development of organ-specific autoimmunity, namely the breakdown in self-tolerance. Here we review the major immune-modulating genes that are associated with AITD and their potential functional effects on thyroidal immune dysregulation.     

炎性及炎性脱髓鞘性脊髓病变临床及实验室检查分析

目的了解不同病因导致的炎性及炎性脱髓鞘性脊髓病变临床特点及实验室检查结果。方法对62例炎性及炎性脱髓鞘性脊髓病变病人的临床资料进行回顾性分析。62例中非特异性脊髓病变（NSM组）18例,多发性硬化（MS）相关性脊髓病变10例,视神经脊髓炎（NMO）相关性脊髓病变29例,其他自身免疫相关性脊髓病变5例。结果 4组发病年龄、性别、诱发因素差异无显著性（P〉0.05）。临床表现中NSM组肢体躯干疼痛例数高于其他3组,差异有显著性（P=0.045）,其他症状和体征4组比较差异无显著性（P〉0.05）。4组脊髓MRI受累节段大于3个例数及病灶节段长度比较,差异有显著性（P=0.000 1;F=5.658,P〈0.05）;4组单纯颈髓、单纯胸髓、颈胸联合受累例数比较,差异无显著性（P〉0.05）。实验室及电生理检查结果显示,4组OCB、血清NMO-IgG阳性、甲状腺功能异常、抗SSA/SSB阳性、抗核抗体阳性、Ro-52阳性、VEP异常例数比较,差异有显著性（P=0.001～0.015）;而脑脊液细胞数异常、蛋白异常、肝炎三对半异常、ENA阳性、SEP异常、BAEP异常例数比较,差异无显著性（P〉0.05）。结论躯干疼痛、NMO-IgG抗体阳性、脊髓MRI病变大于3个节段、甲状腺功能异常以及VEP异常可作为NMO诊断和鉴别诊断依据;OCB阳性可作为MS鉴别诊断依据,抗SSA/SSB阳性、抗核抗体阳性、Ro-52阳性更支持自身免疫性疾病诊断。     

以顽固性呃逆和恶心呕吐为首发症状的视神经脊髓炎临床分析

目的 研究以顽固性呃逆和恶心呕吐(IHN)为首发症状的视神经脊髓炎(NMO)的临床特点及MRI表现.方法 收集50例NMO患者的临床资料,对其中5例以IHN为首发症状的NMO患者临床表现及MRI特点进行分析.结果 以IHN为首发症状的NMO患者女性多见,发病较晚,头MRI显示病灶主要分布在第三、四脑室,中脑导水管周围及延髓中央管等室管膜周边,脊髓MRI显示线样延髓脊髓损害,病灶常常为大于3个椎体节段,主要累及灰质,以脊髓中央管为中心呈H型分布.结论 IHN是NMO的独特首发症状,并完全可逆,主要累及孤束核和最后区引起IHN.其MRI病灶具有特异性,多分布在室管膜和脊髓中央管周边(即水通道蛋白4的高表达区),呈线样损害.     

Detection of anti-aquaporin-4 autoantibodies in the sera of Chinese neuromyelitis optica patients

In this study, we recruited 10 neuromyelitis optica patients, two multiple sclerosis patients and two myelitis patients. Chinese hamster lung fibroblast (V79) cells transfected with a human aquaporin-4-mCherry fusion protein gene were used to detect anti-aquaporin-4 antibody in neuromyelitis optica patient sera by immunofluorescence. Anti-aquaporin-4 autoantibody was stably detected by immunofluorescence in neuromyelitis optica patient sera exclusively. The sensitivity of the assay for neuromyelitis optica was 90% and the specificity for neuromyelitis optica was 100%. The anti-aquaporin-4 antibody titers in sera were tested with serial dilutions until the signal disappeared. A positive correlation was detected between Expanded Disability Status Scale scores and serum anti-aquaporin-4 antibody titers. The anti-aquaporin-4 antibody assay is highly sensitive and specific in the sera of Chinese neuromyelitis optica patients. Detection of aquaporin-4 autoantibody is important for the diagnosis and treatment of neuromyelitis optica.     

Neuromyelitis optica spectrum disorders may be misdiagnosed as Wernicke's encephalopathy

Purpose: To raise doctors’ attention to the differential diagnosis of neuromyelitis optica spectrum disorders (NMOSD) and Wernicke's encephalopathy (WE). Patients and methods: We extensively reviewed the medical records of 136 patients who had visited our hospital since 2008 and were suspected of having central nervous system demyelinating diseases. Four of those patients had somnolence, electrolyte imbalance and brain lesions around the third ventricle and were included in the study. We tested the serum of the four patients for the presence of aquaporin-4 (AQP4) M23 antibody. Results: All the four patients had positive AQP4 antibody in their serum. Two of the patients were misdiagnosed as WE before AQP4 antibody detection occurred. Conclusions: NMOSD and WE have similar brain lesion locations, histopathological changes and clinical manifestations. It is important to distinguish NMOSD from WE by detecting AQP4 antibody in serum or cerebral spinal fluid. Vitamin B1 should also be administered to the patients who have a history of thiamine deficiency.     

Horner Syndrome in a Case of Neuromyelitis Optica

A 58-year-old right-handed woman presented with neck pain and right hemibody decreased pain and temperature sensation. Over the next 3 days, she developed left ptosis and miosis. The Horner syndrome was confirmed with 0.5% apraclonidine and neuromyelitis optica immunoglobulin G antibody titres were positive. Magnetic resonance imaging of the cervical spine showed a longitudinally extensive intramedullary expansile lesion more prominent on the left, with post-contrast enhancement extending from C2 to C5, consistent with neuromyelitis optica. This patient was diagnosed with neuromyelitis optica with an associated left Horner syndrome.     

Lesions of the posterior limb of the internal capsule in neuromyelitis optica spectrum disorder

Posterior limb of the internal capsule lesions (PLICL) are one of the MRI features of neuromyelitis optica spectrum disorder (NMOSD). However, there is no evidence that such lesions are pathogenically related to NMOSD. We retrospectively analyzed features of PLICL in NMOSD, and other central nervous system inflammatory disorders, in 561 patients. We also examined the pathological samples of six patients. Of the 561 patients investigated, PLICL were found in 65 patients (11.6%). Lesions were bilateral in 26 cases (40%) and unilateral in 39 cases (60%). Unilateral lesions were mainly located on the left side (74.3%, 29/39). Of the 65 patients with PLICL, 46 patients had NMOSD (70.8%) and were positive for anti-aquaporin (AQP4-IgG), four had NMOSD (6.2%) and were AQP4-IgG negative, 10 patients had multiple sclerosis (MS), three patients had NMDAR encephalitis, and two had autoimmune meningoencephalitis. Of the six patients whose pathological samples were evaluated, all had PLICL and were negative for AQP4-IgG, and none had pathological NMOSD lesion features. These cases included three patients with multiple sclerosis, one with anti-N-methyl-D-aspartate receptor encephalitis, and two with autoimmune meningoencephalitis. In conclusion, PLICL are found not only in patients with NMOSD, but also in MS and other disorders.     

Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis

Autoimmune associations in myasthenia gravis (MG)-patients and their relatives have not been re-assessed since their separation into early- or late-onset MG (EOMG, LOMG), or thymoma-associated MG.