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.     

脑脊液MOG抗体阳性的视神经脊髓炎谱系疾病患者的临床特征

目的探讨MOG抗体阳性的NMOSD患者的临床特点。方法选择29例NMOSD患者,根据血清AQP-4抗体以及脑脊液MOG抗体检测结果,分为MOG抗体阳性、AQP4抗体阳性的NMOSD(剔除双阳性者),同时选择13例MS患者作为对照。回顾性分析上述三组患者临床信息,统计归纳其临床特点。结果 29例NMOSD患者中血清AQP4抗体阳性者11例,脑脊液MOG抗体阳性者8例。36.4%(4例/11例)AQP4抗体阳性、62.5%(5例/8例)MOG抗体阳性NMOSD患者,以及7.7%(1例/13例)MS患者合并脊髓炎与视神经炎,三组间差异有统计学意义(χ~2=7.128,P=0.028),其中MOG抗体阳性NMOSD患者较MS患者更易合并视神经炎(χ~2=7.289,P=0.014)。MOG抗体阳性NMOSD患者缓解期EDSS分数低于AQP4抗体阳性NMOSD患者[3.50(2.50,4.00),4.00(3.50,6.00),Z=-2.379,P=0.020]。MOG抗体阳性NMOSD脊髓病灶多表现为多发的长节段脊髓病灶,50%(4例/8例)MOG抗体阳性脊髓病灶个数大于1个,与MS组无明显差异,而AQP4抗体阳性组均为单个病灶。MOG抗体阳性NMOSD脊髓病灶长度较AQP4抗体阳性组短[分别(3(2,3)个椎体、4(3,5)个椎体,Z=-2.499,P=0.012],较MS组[(1.25(1,1.5)个椎体]长(Z=-3.447,P0.001)。8例MOG抗体阳性患者中5例存在颅内病灶,3例表现为NMOSD样颅内病灶,余2例表现为MS样颅内病灶,其病灶形态及部位与AQP4抗体阳性组无明显差异,而与MS组存在差异。结论 MOG抗体阳性NMOSD合并视神经炎的患者较多,临床残障程度较轻,预后较好,脊髓病灶为多发的长节段脊髓病灶;颅内病灶的形态及部位与MS无明显差异。     

Brain magnetic resonance imaging abnormalities in neuromyelitis optica

Objective – Brain abnormalities in neuromyelitis optica (NMO) attracted much attention. Our study was to identify the brain magnetic resonance imaging (MRI) abnormalities in Chinese NMO patients. Methods – Patients who fulfilled the latest diagnostic criteria of NMO proposed by Wingerchuk et al. [Neurology 66 (2006) 1485] and whose brain MRI did not meet the multiple sclerosis (MS) criteria of McDonald et al. [Ann Neurol 50 (2001) 121] were selected to perform MRI scanning of the brain, spinal cord and optic nerves. Results – Twenty‐eight of 33 patients (84.8%) had abnormal MRI findings. Twenty‐two patients (66.7%) presented with well‐defined brain parenchymal lesions and the other six patients (18.2%) with macroscopic symmetrical diffuse hyperintensities in deep white matter. Fifteen of 22 patients had more than one lesion (≥2 lesions) and the other seven patients had single lesion. In the supratentorium, most lesions were punctate or small round dot and non‐specific in juxtacortical, subcortical and deep white matter regions, a few were patchy atypical confluent lesions. Brainstem was easily involved (14/33, 42.4%) especially in medulla (7/33, 21.2%). Conclusions – This study demonstrates the characteristics of brain MRI abnormalities in Chinese NMO patients, which are helpful to the revision of diagnostic criteria for NMO.     

视神经脊髓炎患者血清 NMO-IgG 检测及其诊断价值

目的 检测神经脊髓炎(neuromyelitis optica,NMO)患者血清NMO-IgG的表达,并探讨其在NMO诊断中的价值.方法 收集北京、辽宁丹东、山西大同三家医疗机构临床诊断为NMO患者26例、多发性硬化(multiple sclerosis,MS)患者32例、神经科其他疾病患者77例;以稳定表达人源水通道蛋白-4(aquaporin-4,AQP4)的人胚肾293(HEK293)细胞株为底物,应用间接免疫荧光法检测患者血清NMO-IgG水平.结果 16例(61.5%)NMO患者血清NMO-IgG阳性,其阳性检出率显著高于MS患者(9.4 %)和MS+神经科其他疾病患者(4.6 %)(P<0.01).NMO-IgG对NMO诊断的灵敏度为61.5%,以MS作为对照时,该抗体对NMO诊断特异度为90.6%,以MS+神经科其他疾病作对照时,其特异度为95.4%.结论 NMO患者血清中普遍存在NMO-IgG,其可作为国内NMO诊断的重要生物学指标.     

视神经脊髓炎患者血浆纤维蛋白原水平及临床相关性分析

目的探讨视神经脊髓炎患者血浆纤维蛋白原(FIB)水平并分析其与临床特点的相关性。方法选择59例NMO患者、56例MS患者、9例AM患者,以19例良性发作性位置性眩晕(BPPV)患者为对照组,采用扩展残疾状态量表(EDSS)评估疾病严重程度,测定并比较各组血浆凝血酶原时间(PT),活化部分凝血酶时间(APTT)、FIB水平、凝血酶时间(TT)及其与临床特点的相关性。结果 NMO急性期患者血浆FIB水平高于MS组(F=18.857,P0.01)及对照组(F=12.238,P0.01)。NMO组血浆FIB水平与EDSS分值相关(r=0.561,P0.01),与患者发病年龄正相关(r=0.340,P=0.008);MS组血浆FIB水平与EDSS分值显著相关(r=0.302,P=0.0024),与疾病病程正相关(r=0.329,P=0.013)。结论视神经脊髓炎发病急性期血浆FIB水平增高并与疾病严重程度呈正相关。     

视神经脊髓炎谱系病患者疼痛的初步研究

目的初步探讨视神经脊髓炎谱系病(NMOSD)患者相关的疼痛问题。方法收集57例NMOSD患者和51例多发性硬化(MS)患者的临床资料,采用数字疼痛强度量表(NRS)对患者疼痛程度及部位进行评估,对比分析两组疼痛发生情况、严重程度、部位及治疗情况。结果 NMOSD组患者疼痛发生率明显高于MS组患者(63.16%vs.35.29%,χ2=8.359,P=0.004)。NMOSD组患者痛性痉挛发生率与MS组差异无统计学意义(24.56%vs.11.76%,χ2=2.921,P=0.087)。NMOSD组患者的疼痛评分在0~8分,以中度疼痛为主[20例(55.56%)],MS组患者的疼痛评分在0~7分,以轻度疼痛为主[11例(61.11%)],但两组间轻度疼痛与中重度疼痛患者比例差异无统计学意义(36.11%vs.61.11%,63.89%vs.38.89%,χ2=3.038,P=0.081)。NMOSD组[16例/36例(44.44%)]及MS组[6例/18例(33.33%)]患者的疼痛部位均以躯干部位最常见。Logistic逐步回归分析显示NMOSD患者的疼痛程度与患者的性别、年龄、病程、发作次数、NMO-IgG及EDSS评分无相关性。结论疼痛在NMOSD患者中十分常见,其疼痛应受到重视,并应积极对症治疗。     

ELISA与FACS定量方法检测血清AQP4抗体诊断NMO的Meta分析

目的系统评价酶联免疫吸附试验(ELISA)、流式细胞术(FACS)检测血清水通道蛋白4抗体(AQP4-IgG)对诊断视神经脊髓炎(NMO)的准确性。方法检索国内外公开发表的相关文献。根据题目、摘要、全文逐步筛选,采用质量评价工具(QUADAS)分析文献质量。采用Meta-Disc1.4与STATA 12.0软件进行Meta分析。根据Meta分析结果综合评价ELISA和FACS方法诊断NMO的准确性。结果经过严格的纳入及排除标准,最终纳入17篇文献。ELISA和FACS方法合并敏感度分别为0.63(95%CI:0.58~0.68)和0.55(95%CI:0.48~0.61),合并特异度分别为0.98(95%CI:0.97~0.98)和0.99(95%CI:0.98~0.99)。拟合受试者工作特征曲线(SROC),得到SROC曲线下面积(AUC)分别为0.9521和0.9542。结论通过ELISA和FACS方法检测AQP-4-IgG对于诊断NMO特异度高,两者都具有较高的诊断效能和准确率。但受纳入研究质量和数量限制,两种方法诊断效能的一致性尚需开展更多高质量研究予以验证。     

Clinical and pathological features of Devic’s neuromyelitis optica and multiple sclerosis in Chinese patients

BACKGROUND:Devic's neuromyelitis optica (DNMO) and multiple sclerosis in Asian populations have been considered to be the same disease. However, there is an increasing number of studies suggesting that DNMO and multiple sclerosis are different diseases.OBJECTIVE:Little information is available regarding comparisons of DNMO patients between China and other countries, as well as clinical manifestations of Chinese patients with DNMO and multiple sclerosis. The present study performed a multi-center, pathological, retrospective analysis.DESIGN, TIME AND SETTING:A retrospective analysis of clinical data from seven patients with DNMO diagnosed between 1957 and 1998.PARTICIPANTS:Data from Chinese DNMO patients was provided by the Shanghai Second Medical University, Sun Yat-sen University of Medical Sciences and the First Affiliated Hospital of Harbin Medical University in China.METHODS:Clinical and pathological data from Chinese patients with DNMO were retrospectively analyzed. The clinical characteristics of DNMO were compared between Chinese and Caucasian patients. In addition, clinical and pathological differences between DNMO and multiple sclerosis Chinese patients were compared.MAIN OUTCOME MEASURES:Clinical and pathological features of Chinese patients with DNMO.RESULTS:All seven Chinese patients with DNMO exhibited abrupt onset of vision disturbance, with a disease course of 3 clays to 9 years. DNMO recurred in two of the patients. Demyelinating lesions were observed in all patients, with necrotic lesions and gitter cells in five patients, collagenous hyperplasia in one patient, and perivascular inflammatory cell infiltration in six patients. Comparison between Chinese and Caucasian DNMO patients revealed no significant differences in age at onset, clinical onset, duration, or interval between optic neuritis and myelitis. Compared with Chinese multiple sclerosis patients, Chinese DNMO patients presented with fewer recurrences, higher occurrence of necrosis, perivascular inflammatory cell infiltration and gitter cells, and a lower occurrence of collagenous hyperplasia.CONCLUSION:There was no difference in DNMO clinical features between Chinese and Caucasian patients. However, the clinical and pathological features of DNMO were different compared with multiple sclerosis in Chinese patients. Results suggested that the characteristics of DNMO in Chinese patients were significantly different than multiple sclerosis.     

Variants in the promoter region of CYP7A1 are associated with neuromyelitis optica but not with multiple sclerosis in the Han Chinese population

Multiple sclerosis（MS）and neuromyelitis optica（NMO）are common autoimmune demyelinating disorders of the central nervous system.The exact etiology of each remains unclear.CYP7A1was reported to be associated with NMO in Korean patients,but this is yet to be confirmed in other populations.In this study,we used Sanger sequencing to detect SNPs in the promoter region of CYP7A1 in a population consisting of unrelated patients and controls from the Han Chinese population（129 MS;89 NMO;325 controls）.Two known SNPs,204A〉C（rs3808607）and 469T〉C（rs3824260）,and a novel SNP（208G〉C）were identified in the 5＇-UTR of CYP7A1.The 204A〉C was in complete linkage with 469T〉C and both were associated with NMO but not with MS.Results suggest that the CYP7A1 allele was associated with NMO.NMO and MS have different genetic risk factors.This further supports the emerging evidence that MS and NMO are distinct disorders.     

视神经脊髓炎与多发性硬化的临床症状、脊髓MRI表现的对比分析

目的 结合视神经脊髓炎(NMO)与多发性硬化(MS)患者的临床症状和脊髓MRI特点探讨两者之间差异发生的机制.方法 回顾性分析中山大学附属第三医院自2004年1月至2007年1月收治的23例NMO患者及21例MS患者的临床资料,比较其临床症状及脊髓MRI上受损部位MRI上的差异.结果 NMO患者多为女性,且首次发病年龄、扩展病残状况评分(EDSS)评分均高于MS患者;双侧深感觉障碍、束带感、直肠或膀胱括约肌功能障碍3种临床症状在NMO、MS患者中的发生率不同,差异均有统计学意义(P<0.05);上述各临床症状基本能在脊髓MRI找到相应受损病灶.结论 NMO是不同于MS的脱髓鞘疾病,其特殊的发病机制导致其临床症状与脊髓MRI均有自己的特点.     

Hypothalamic abnormality in patients with inflammatory demyelinating disorders

Background: Hypothalamic lesions in neuromyelitis optica (NMO) patients might be more specific for NMO than multiple sclerosis (MS). However, this is controversial. Objective: To characterize clinical features of patients with inflammatory demyelinating disorders (IDDs) with visible hypothalamic lesions using magnetic resonance imaging (MRI). Methods: Patients with IDDs (n = 429) were recruited retrospectively. Results: Of 52 patients with hypothalamic images enrolled, 42 were positive for aquaporin-4 (AQP4) antibodies, including 28 patients with NMO, 6 with recurrent transverse myelitis, 3 with recurrent optic neuritis, and 5 with brainstem and brain syndrome. The remaining 10 patients were anti-AQP4-negative, including 3 with MS, 3 with acute disseminated encephalomyelitis, and 4 with other disorders. In the AQP4-positive group, manifestations, including ataxia, intractable hiccup and nausea, syndrome of inappropriate antidiuretic hormone secretion and encephalopathy were more frequent in those with hypothalamic lesions than those without. Cell counts of cerebrospinal fluid in patients with hypothalamic lesions differed from patients without lesions. Brain MRI abnormalities were more frequent in brainstem and hemisphere of the hypothalamic lesion group. Conclusions: Hypothalamic lesions were observed frequently in patients with AQP4 antibodies. Clinical manifestations and paraclinical features in AQP4-positive patients with hypothalamic lesions differed from those without lesions.     

Coexistence of myasthenia gravis and serological markers of neurological autoimmunity in neuromyelitis optica

We systematically evaluated the frequency of neurological disorders and muscle and neural autoantibodies in 177 patients with neuromyelitis optica (NMO) and in 250 control subjects (173 healthy; 77 multiple sclerosis, MS, patients). An excess of myasthenia gravis (MG, 2%), and muscle‐type acetylcholine receptor antibody (11%) was detected among NMO patients. The presence of neural or muscle autoantibodies was more common in NMO patients (34%) than in MS patients or healthy controls (7%), P < 0.0001. The coexistence of NMO and MG should be considered in atypical or refractory presentations of either disorder. © 2008 Wiley Periodicals, Inc. Muscle Nerve 39: 87–90, 2009     

Review: Recent advances in the understanding of the pathophysiology of neuromyelitis optica spectrum disorder

Neuromyelitis optica is an autoimmune inflammatory disorder of the central nervous system that preferentially targets the spinal cord and optic nerve. Following the discovery of circulating antibodies against the astrocytic aquaporin 4 (AQP4) water channel protein, recent studies have expanded our knowledge of the unique complexities of the pathogenesis of neuromyelitis optica and its relationship with the immune response. This review describes and summarizes the recent advances in our understanding of the molecular mechanisms underlying neuromyelitis optica disease pathology and examines their potential as therapeutic targets. Additionally, we update the most recent research by proposing major unanswered questions regarding how peripheral AQP4 antibodies are produced and their entry into the central nervous system, the causes of AQP4-IgG-seronegative disease, why peripheral AQP4-expressing organs are spared from damage, and the impact of this disease on pregnancy.