视神经脊髓炎谱系疾病二例

视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders,NMOSDs)特指一组潜在发病机制与视神经脊髓炎(neuromyelitis optica,NMO)相近,但临床受累局限不完全符合NMO诊断的相关疾病.NMOSDs临床表现多样,易造成误诊. 1 病例报告 病例1:患者女,24岁,以"反复纳差伴呕吐3个月,视物模糊、步态不稳半个月"入院.患者3个月前渐出现食欲下降伴顽固性呕吐.曾在消化内科拟诊为反流性食管病,行对症治疗但无明显改善;半个月前出现视物模糊,步态不稳.无幻觉及力弱,无吞咽困难及呛咳,无尿便障碍.     

视神经脊髓炎谱系疾病合并系统性红斑狼疮的临床特征分析

视神经脊髓炎谱系疾病( neuromyelitis optica spectrum disorder,NMOSD)是一种主要累及视神经及脊髓的中枢神经系统炎性脱髓鞘疾病,其发病主要与水通道蛋白 4 抗体( AQP4-IgG)介导的自身免疫应答反应有关[1].系统性红斑狼疮( systemic lupus erythem...     

视神经脊髓炎谱系疾病合并系统性红斑狼疮的临床特征分析

视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorder,NMOSD)是一种主要累及视神经及脊髓的中枢神经系统炎性脱髓鞘疾病,其发病主要与水通道蛋白4抗体(AQP4-IgG)介导的自身免疫应答反应有关[1].系统性红斑狼疮(systemic lupus erythematosu...     

视神经脊髓炎谱系疾病1例报道并文献复习

目的提高对视神经脊髓炎谱系疾病(NMOSD)的认识。方法报道1例以脑干症状为首发、继以急性横贯性脊髓炎的NMOSD患者,结合文献复习进行分析。结果青年女性患者,发病时表现为左侧味觉减退以及左侧面部瘙痒,继以出现急性横贯性脊髓炎。MRI显示延髓右侧和左侧桥脑被盖部、中脑导水管周围长T1、长T2信号病灶,脊髓MRI显示颈1~5长T2信号病灶;血清水通道蛋白4(AQP4)抗体阳性。患者符合AQP4抗体阳性NMOSD的诊断标准。结论 NMOSD常有脑部症状,尤其是脑干症状。部分患者可以脑干症状为首发临床表现,对此类患者应及早行AQP4抗体检测,以明确诊断及早干预。     

120例视神经脊髓炎谱系疾病临床特点分析

目的基于2015年诊断标准分析视神经脊髓炎谱系疾病(NMOSD)患者的临床特点和影像学特征。方法回顾性分析120例NMOSD患者的临床特点、影像学特征、以及对比水通道蛋白4(AQP4)抗体阳性和阴性患者的临床异同点。结果女性∶男性=2.75∶1,平均发病年龄37.1岁,平均病程21个月,80%患者为复发病程。起病症状视神经炎和脊髓炎分别占41.7%和40%。15.8%患者伴有自身免疫病;5.8%患者伴有内分泌疾病。78.1%的患者AQP4抗体阳性,抗体阳性组疾病严重程度评分显著高于抗体阴性组(P=0.026)。长节段横贯性脊髓炎占83.7%。头部MRI异常见于36.7%(44/120)患者。28.3%(34/120)患者脑脊液白细胞升高(5×10~6/L),脑脊液蛋白49.5 mg/dl(正常值:15~45 mg/dl);30.8%(37/120)患者寡克隆区带阳性;52.2%(24/46)患者髓鞘碱性蛋白阳性;40%(48/120)患者脑脊液免疫球蛋白G升高。结论 2015年诊断标准有助于NMOSD诊断,NMOSD长节段脊髓炎多见,短节段脊髓炎不能排除NMOSD,AQP4抗体阳性患者病情更重,应重视早期诊断。     

补体靶向药物治疗AQP4-IgG阳性视神经脊髓炎谱系疾病的进展

视神经脊髓炎谱系疾病(NMOSD)是一种严重的炎症性脱髓鞘疾病,75%NMOSD患者体内存在针对中枢神经系统水通道蛋白4(AQP4)的致病性抗体(AQP4-IgG)。补体系统是一组存在于人和动物血清及组织液、细胞膜表面的经活化后具有生物活性的蛋白质。近年来,随着对NMOSD致病机制的研究不断深入,补体系统被发现在AQP4-IgG阳性NMOSD发生发展中具有重要作用,并且参与机体免疫调节。目前,针对自身免疫性疾病的补体靶向药物陆续被研发,部分已应用于AQP4-IgG阳性NMOSD患者的治疗。文中就AQP4-IgG阳性NMOSD补体靶向药物治疗的研究进展展开综述。     

首次检测水通道蛋白-4抗体阴性视神经脊髓炎谱系疾病的临床转归

目的分析水通道蛋白-4抗体(aquaporin-4 immunoglobulin G antibodies,AQP4-IgG)阴性的视神经脊髓炎谱系疾病(neuro myelitis optica spectrum disorder,NMOSD)患者临床特征、抗体演变以及转归。方法纳入中山大学附属第三医院神经科首次检测AQP4-IgG阴性的NMOSD患者15例,定期门诊随访,收集临床及实验室检查资料,分析其临床转归。结果 15例AQP4-IgG阴性患者平均随诊67个月,以视神经炎(optic neuritis,ON)症状起病最多见(8例)。动态复查血清AQP4-IgG,其中4例(27%)由阴性转为阳性,2例血清不稀释处理时显示极低滴度(滴度为1:1)阳性,9例持续阴性。随访中,1例患者最终修正诊断为多发性硬化,4例诊断为AQP4-IgG阳性NMOSD。AQP4-IgG从阴性转变为阳性的时间节点临床可无复发(1例),但持续阴性患者也出现临床复发(3例)。结论 AQP4-IgG阴性NMOSD患者最常累及视神经;临床随访中AQP4-IgG可能发生血清学转变,患者诊断及转归不同。     

免疫吸附治疗视神经脊髓炎谱系病患者的临床分析

目的 探讨免疫吸附对视神经脊髓炎谱系病(neuromyelitis optica spectrum disorder, NMOSD)急性期的治疗效果。方法 对15例对大剂量糖皮质激素治疗反应不佳的NMOSD急性发作期患者,进行免疫吸附治疗5次,比较治疗前后的扩展残疾评分量表(expanded disability status scale, EDSS)、视力分层、水通道蛋白4(aquaporin 4,AQP4)抗体水平、免疫球蛋白及补体变化。结果 15例患者免疫吸附治疗后相对于治疗前的EDSS评分[4.0(3.0,6.0)比4.5(3.0,6.5),t=2.640,P=0.008]、AQP4抗体水平[(16.27±22.40)u/mL比(45.24±32.97)u/mL,t=4.011,P=0.002]均显著降低。10例患者共15只眼出现视神经炎,治疗后视力均较治疗前显著改善[视力分层4.0(3.0,5.0)比5.0(3.0,7.0),t=2.872,P=0.007]。免疫吸附治疗后较治疗前补体C3水平[(0.53±0.20)g/L比(1.02±0.22)g/L,t=6.588,P=0...     

2015年视神经脊髓炎谱系疾病诊断标准临床应用评估

目的 评估2015年视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorder,NMOSD)诊断标准的临床应用.方法 回顾性分析作者医院2008-3-2016-8收治的605例中枢神经系统脱髓鞘疾病患者临床资料,并分别采用2015年NMOSD诊断标准及2006年NMO诊断标准对其进行诊断分析.结果 共有176例患者符合2015年NMOSD诊断标准,其中108例(61.4％)符合2006年NMO诊断标准.AQP4-IgG阳性患者139例(79.0％).当假设该139例患者AQP4-IgG水平未知时,共有91例(65.5％)符合2015年NMOSD诊断标准,而仅有55例(39.6％)满足2006年NMO诊断标准(P＜0.05).176例患者中有39例同时满足2006年NMO诊断标准和201 5年NMOSD诊断标准且以临床孤立病灶起病,在疾病早期通过2006年NMO诊断标准尚不能与多发性硬化相鉴别,但已符合2015年NMOSD诊断标准.在核心症状方面,NMOSD患者中以急性脊髓炎(50.6％)和视神经炎(31.8％)起病者所占比例最高,其次为最后区综合征(5.7％).结论 2015年NMOSD诊断标准较2006诊断标准扩大了疾病的诊断范围,且在AQP4-IgG水平未知的情况下仍具有更高的诊断敏感性,对于疾病早期与多发性硬化的鉴别中具有重要作用,且更加强调了疾病的核心症状.     

视神经脊髓炎谱系病维持治疗研究进展

视神经脊髓炎谱系病(NMOSD)是严重的致残性中枢神经系统自身免疫性疾病.多为复发型病程,残疾进展呈发作依赖性,预防复发NMOSD的维持治疗是缓解期治疗的关键.2019年起NMOSD维持治疗取得突破性进展,3种靶向药物相继获批适应证.当前维持治疗种类繁多,传统的超适应证和新型药物的适应证并存,尚缺乏对相关研究的总结.文...     

Targeting Neuromyelitis Optica Pathogenesis: Results from Randomized Controlled Trials of Biologics

Advances in neuromyelitis optica spectrum disorder pathogenesis have allowed the development of targeted drugs. These treatments act on core elements of the disease, including the pro-inflammatory IL-6 pathway (tocilizumab and satralizumab), B cells (rituximab and inebilizumab), and complement (eculizumab). According to recent phase II–III trials, biologics significantly reduced the risk of relapses in aquaporin-4-seropositive patients, whereas results were less striking in the small cohorts of aquaporin-4-seronegative patients. Most adverse events were mild to moderate, with systemic symptoms (headache, arthralgia) or infections (upper respiratory and urinary tracts) being most commonly reported.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01055-0.     

Biotinidase deficiency presenting as Neuromyelitis Optica Spectrum Disorder

Biotinidase deficiency disorder is a rare inherited metabolic disorder with typical neurological manifestations of hypotonia, developmental delay, rashes, seizures, hearing and vision impairment. We present two cases with different and unusual clinical profiles, whose neuroimaging resembled Neuromyelitis Optica Spectrum Disorder. Case 1 was initially treated with immunomodulation with steroids and intravenous immunoglobulins, with partial improvement. However reinvestigation for worsening of symptoms showed more extensive changes on spine magnetic resonance imaging. Raised lactate and alanine levels on repeat cerebrospinal fluid testing resulted in further investigations that revealed a biotinidase deficiency. Case 2 presented mainly with respiratory symptoms: a barium swallow suggested bulbar dysfunction. Neuroimaging of brain and spine was similar to that in case 1 and the child was promptly investigated for and confirmed to have biotinidase deficiency. Both cases responded to biotin supplementation. It is important to be cognisant of atypical neurological presentations of biotinidase deficiency including those that mimic immune mediated neurodemyelination disorders, as biotinidase deficiency is potentially treatable.     

Neuromyelitis Optica Preceded by Brain Demyelinating Episode

Neuromyelitis optica (NMO) is considered a distinct disease from multiple sclerosis (MS) because of its pathogenesis. It is well accepted that NMO selectively affects the spinal cord and optic nerve and is not associated with brain lesions at the onset of the disease, unlike MS. We present a unique case where the patient's initial lesion was in the brain, and optic neuritis and myelitis were revealed 6 years after the brain lesion. In addition, the patient's serum antiaquaporin 4 (AQP4) antibody was positive. We consider the brain lesion to precede abnormal lesion of NMO, and the AQP4 measurement is important for diagnostics, even if it occurs with brain lesions.     

An Update on the Laboratory Diagnosis of Neuromyelitis Optica Spectrum Disorders

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder of the central nervous system that is specifically associated with demyelination of spinal cord and optic nerves. The discovery of specific autoantibody markers such as aquaporin-4 IgG and myelin oligodendrocyte glycoprotein IgG has led to several methodologies being developed and validated. There have been numerous investigations of the clinical and radiological presentations used in the clinical diagnosis of NMOSD. However, although various laboratory diagnostic techniques have been standardized and validated, a gold-standard test has yet to be finalized due to uncertain sensitivities and specificities of the methodologies. For this review, the literature was surveyed to compile the standardized laboratory techniques utilized for the differential diagnosis of NMOSD. Enzyme-linked immunosorbent assays enable screening of NMOSD, but they are considered less sensitive than cell-based assays (CBAs), which were found to be highly sensitive and specific. However, CBAs are laborious and prone to batch variations in their results, since the expression levels of protein need to be maintained and monitored meticulously. Standardizing point-of-care devices and peptide-based assays would make it possible to improve the turnaround time and accessibility of the test, especially in resource-poor settings.     

Cerebral Cortex Involvement in Neuromyelitis Optica Spectrum Disorder

MethodsThe study enrolled 215 NMOSD patients who were seropositive for the anti-AQP4 antibody from 5 referral hospitals, and retrospectively analyzed their demographic, clinical, and MRI findings. Abnormal cerebral cortex lesions on brain MRI were identified by a neuroradiologist and two neurologists using consensus.ResultsMost of the 215 enrolled patients (87%) were female. The median age at onset was 22.5 years (range: 15–36 years) and the mean follow-up duration was 123 months. Brain lesions were found in 143 of 194 patients (74%) in whom MRI was performed during follow-up. Brain lesions involving the cerebral cortex were identified in 6 of these 194 patients (3.1%). Five of the patients were female, and the six patients together had a median age of 29 years (range: 15–36 years) at the time of lesion presentation. Three of them showed leptomeningeal enhancement in the lesions. At presentation of the cortex-involving lesions, five of these patients were not being treated at the time of presentation, while the sixth was being treated with interferon-beta.ConclusionsAlthough rare, cortical involvement occurs in NMOSD and is commonly combined with leptomeningeal enhancement. We speculate that this occurs only in patients who are not treated appropriately with immunosuppressant drugs.     

P2R Inhibitors Prevent Antibody-Mediated Complement Activation in an Animal Model of Neuromyelitis Optica: P2R Inhibitors Prevent Autoantibody Injury

Purinergic 2 receptors (P2Rs) contribute to disease-related immune cell signaling and are upregulated in various pathological settings, including neuroinflammation. P2R inhibitors have been used to treat inflammatory diseases and can protect against complement-mediated cell injury. However, the mechanisms behind these anti-inflammatory properties of P2R inhibitors are not well understood, and their potential in CNS autoimmunity is underexplored. Here, we tested the effects of P2R inhibitors on glial toxicity in a mouse model of neuromyelitis optica spectrum disorder (NMOSD). NMOSD is a destructive CNS autoimmune disorder, in which autoantibodies against astrocytic surface antigen Aquaporin 4 (AQP4) mediate complement-dependent loss of astrocytes. Using two-photon microscopy in vivo, we found that various classes of P2R inhibitors prevented AQP4-IgG/complement-dependent astrocyte death. In vitro, these drugs inhibited the binding of AQP4-IgG or MOG-IgG to their antigen in a dose-dependent manner. Size-exclusion chromatography and circular dichroism spectroscopy revealed a partial unfolding of antibodies in the presence of various P2R inhibitors, suggesting a shared interference with IgG antibodies leading to their conformational change. Our study demonstrates that P2R inhibitors can disrupt complement activation by direct interaction with IgG. This mechanism is likely to influence the role of P2R inhibitors in autoimmune disease models and their therapeutic impact in human disease. Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01269-w.