Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Department of Neurology, Second Faculty of Medicine, Charles University, Motol University Hospital, Prague, Czech Republic.
Ann Neurol. 2021 Apr;89(4):698-710. doi: 10.1002/ana.26013. Epub 2021 Jan 27.
Diagnosing autoimmune encephalitis (AIE) is difficult in patients with less fulminant diseases such as epilepsy. However, recognition is important, as patients require immunotherapy. This study aims to identify antibodies in patients with focal epilepsy of unknown etiology, and to create a score to preselect patients requiring testing.
In this prospective, multicenter cohort study, adults with focal epilepsy of unknown etiology, without recognized AIE, were included, between December 2014 and December 2017, and followed for 1 year. Serum, and if available cerebrospinal fluid, were analyzed using different laboratory techniques. The ACES score was created using factors favoring an autoimmune etiology of seizures (AES), as determined by multivariate logistic regression. The model was externally validated and evaluated using the Concordance (C) statistic.
We included 582 patients, with median epilepsy duration of 8 years (interquartile range = 2-18). Twenty patients (3.4%) had AES, of whom 3 had anti-leucine-rich glioma inactivated 1, 3 had anti-contactin-associated protein-like 2, 1 had anti-N-methyl-D-aspartate receptor, and 13 had anti-glutamic acid decarboxylase 65 (enzyme-linked immunosorbent assay concentrations >10,000IU/ml). Risk factors for AES were temporal magnetic resonance imaging hyperintensities (odds ratio [OR] = 255.3, 95% confidence interval [CI] = 19.6-3332.2, p < 0.0001), autoimmune diseases (OR = 13.31, 95% CI = 3.1-56.6, p = 0.0005), behavioral changes (OR 12.3, 95% CI = 3.2-49.9, p = 0.0003), autonomic symptoms (OR = 13.3, 95% CI = 3.1-56.6, p = 0.0005), cognitive symptoms (OR = 30.6, 95% CI = 2.4-382.7, p = 0.009), and speech problems (OR = 9.6, 95% CI = 2.0-46.7, p = 0.005). The internally validated C statistic was 0.95, and 0.92 in the validation cohort (n = 128). Assigning each factor 1 point, an antibodies contributing to focal epilepsy signs and symptoms (ACES) score ≥ 2 had a sensitivity of 100% to detect AES, and a specificity of 84.9%.
Specific signs point toward AES in focal epilepsy of unknown etiology. The ACES score (cutoff ≥ 2) is useful to select patients requiring antibody testing. ANN NEUROL 2021;89:698-710.
在癫痫等起病不那么急骤的疾病患者中，诊断自身免疫性脑炎（autoimmune encephalitis，AIE）较为困难。然而，识别该病非常重要，因为患者需要免疫治疗。本研究旨在鉴定病因不明局灶性癫痫患者的抗体，并创建一个评分来初步筛选需要检测的患者。
本前瞻性多中心队列研究纳入了 2014 年 12 月至 2017 年 12 月间病因不明、无公认 AIE 的局灶性癫痫成人患者，并对其进行了为期 1 年的随访。采用不同的实验室技术分析血清和（如可行）脑脊液。采用多变量逻辑回归确定有利于癫痫发作自身免疫病因（antibody contributing to focal epilepsy signs and symptoms，AES）的因素来创建 ACE 评分。通过一致性（concordance，C）统计量对模型进行内部验证和外部验证。
共纳入 582 例患者，中位癫痫病程为 8 年（四分位距=2-18 年）。20 例（3.4%）患者存在 AES，其中 3 例为抗亮氨酸丰富胶质瘤失活 1 抗体阳性，3 例为抗接触蛋白相关蛋白样 2 抗体阳性，1 例为抗 N-甲基-D-天冬氨酸受体抗体阳性，13 例为抗谷氨酸脱羧酶 65 抗体阳性（酶联免疫吸附试验浓度＞10000IU/ml）。AES 的危险因素包括颞叶磁共振成像高信号（优势比[odds ratio，OR] = 255.3，95%置信区间[confidence interval，CI] = 19.6-3332.2，p<0.0001）、自身免疫性疾病（OR = 13.31，95%CI = 3.1-56.6，p = 0.0005）、行为改变（OR = 12.3，95%CI = 3.2-49.9，p = 0.0003）、自主神经症状（OR = 13.3，95%CI = 3.1-56.6，p = 0.0005）、认知症状（OR = 30.6，95%CI = 2.4-382.7，p = 0.009）和言语问题（OR = 9.6，95%CI = 2.0-46.7，p = 0.005）。内部验证的 C 统计量为 0.95，验证队列（n = 128）中为 0.92。每个因素赋值 1 分，抗体贡献局灶性癫痫体征和症状评分（antibodies contributing to focal epilepsy signs and symptoms，ACES）≥2 分具有 100%的敏感性来检测 AES，特异性为 84.9%。
局灶性病因不明癫痫中存在特定的体征提示 AES。ACES 评分（截断值≥2）有助于筛选需要抗体检测的患者。
