N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes.
N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes.
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DOI：
10.1093/brain/awq113
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Vincent A
中科院分区：
文献类型：
--
作者：
Irani SR;Bera K;Waters P;Zuliani L;Maxwell S;Zandi MS;Friese MA;Galea I;Kullmann DM;Beeson D;Lang B;Bien CG;Vincent A
谷氨酸受体n -甲基-d-天冬氨酸亚型抗体与一种新描述的脑病有关，这种脑病主要在患有卵巢肿瘤的年轻女性中发现。然而，完整的临床谱和治疗反应尚不清楚。我们建立了一种基于细胞的灵敏检测血清或脑脊液中n -甲基-d-天冬氨酸受体抗体的方法，以及一种用于系列研究的定量荧光免疫沉淀法。尽管鞘内有明显的n -甲基-d-天冬氨酸受体抗体合成，但血清中n -甲基-d-天冬氨酸受体抗体的绝对水平高于脑脊液。n -甲基-d-天冬氨酸受体抗体属于免疫球蛋白G1亚类，能够激活表达n -甲基-d-天冬氨酸受体的人胚胎肾细胞的补体。从对44名n -甲基-d-天冬氨酸受体抗体阳性患者的问卷调查中，我们发现未检测到肿瘤的比例很高（35/ 44,80%：随访3.6-121个月，中位16个月）。后者中有15名成年女性（43%），10名成年男性（29%）和10名儿童（29%），其中4名在生命的前十年。总体而言，非白种人的比例很高（29%）。良好的临床结果，根据修正Rankin评分的降低来定义，与n-甲基-d-天冬氨酸受体抗体水平的降低相关，并且与非副肿瘤患者早期（<40天）给予免疫治疗（P < 0.0001）和副肿瘤患者早期肿瘤切除（P = 0.02）相关。10例（23%）在复发期间首次诊断的患者没有肿瘤证据，但在早期发作期间接受了很少或没有接受免疫治疗。神经学特征的发病时间分析表明，其进展经历了两个主要阶段。早期特征的发病时间，以神经精神症状和癫痫发作为特征，中间时间为10-20天，开始出现运动障碍，意识减少和自主神经障碍。这种时间上的二分法也见于脑脊液、脑电图和相当罕见的脑成像变化的时间。总的来说，我们的数据支持一个模型，其中早期特征与脑脊液淋巴细胞增多症有关，晚期特征与寡克隆带的出现有关。这些观察结果背后的免疫事件和神经元机制需要进一步探索，但一种可能性是，早期阶段代表血清抗体扩散到皮层灰质，而后期阶段是鞘内隔室免疫库的继发性扩张，作用于皮层下神经元。四名患者，谁只有颞叶癫痫没有寡克隆带，可能代表限制到第一阶段。
Antibodies to the N-methyl-d-aspartate subtype of glutamate receptor have been associated with a newly-described encephalopathy that has been mainly identified in young females with ovarian tumours. However, the full clinical spectrum and treatment responses are not yet clear. We established a sensitive cell-based assay for detection of N-methyl-d-aspartate receptor antibodies in serum or cerebrospinal fluid, and a quantitative fluorescent immunoprecipitation assay for serial studies. Although there was marked intrathecal synthesis of N-methyl-d-aspartate receptor antibodies, the absolute levels of N-methyl-d-aspartate receptor antibodies were higher in serum than in cerebrospinal fluid. N-methyl-d-aspartate receptor antibodies were of the immunoglobulin G1 subclass and were able to activate complement on N-methyl d-aspartate receptor-expressing human embryonic kidney cells. From questionnaires returned on 44 N-methyl-d-aspartate receptor antibody-positive patients, we identified a high proportion without a detected tumour (35/44, 80%: follow-up 3.6–121 months, median 16 months). Among the latter were 15 adult females (43%), 10 adult males (29%) and 10 children (29%), with four in the first decade of life. Overall, there was a high proportion (29%) of non-Caucasians. Good clinical outcomes, as defined by reductions in modified Rankin scores, correlated with decreased N-methyl-d-aspartate receptor antibody levels and were associated with early (<40 days) administration of immunotherapies in non-paraneoplastic patients (P < 0.0001) and earlier tumour removal in paraneoplastic patients (P = 0.02). Ten patients (23%) who were first diagnosed during relapses had no evidence of tumours but had received minimal or no immunotherapy during earlier episodes. Temporal analysis of the onset of the neurological features suggested progression through two main stages. The time of onset of the early features, characterized by neuropsychiatric symptoms and seizures preceded by a median of 10–20 days, the onset of movement disorders, reduction in consciousness and dysautonomia. This temporal dichotomy was also seen in the timing of cerebrospinal fluid, electroencephalographic and in the rather infrequent cerebral imaging changes. Overall, our data support a model in which the early features are associated with cerebrospinal fluid lymphocytosis, and the later features with appearance of oligoclonal bands. The immunological events and neuronal mechanisms underlying these observations need to be explored further, but one possibility is that the early stage represents diffusion of serum antibodies into the cortical grey matter, whereas the later stage results from secondary expansion of the immunological repertoire within the intrathecal compartment acting on subcortical neurons. Four patients, who only had temporal lobe epilepsy without oligoclonal bands, may represent restriction to the first stage.
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影响因子：
9.9
作者：
Graus F;Saiz A;Lai M;Bruna J;López F;Sabater L;Blanco Y;Rey MJ;Ribalta T;Dalmau J
通讯作者：
Dalmau J
影响因子：
9.9
作者：
McKnight, K;Jiang, Y;Lang, B
通讯作者：
Lang, B
影响因子：
11.2
作者：
Dale, Russell C.;Irani, Sarosh R.;Vincent, Angela
通讯作者：
Vincent, Angela
影响因子：
11
作者：
Church, AJ;Dale, RC;Robertson, MM
通讯作者：
Robertson, MM
影响因子：
--
作者：
Castillo, P;Woodruff, B;Boeve, B
通讯作者：
Boeve, B