Abstract:

Objective: To explore the individual features of acute symptomatic seizures across various subtypes of antibody-mediated autoimmune encephalitis (AE), and to identify the influencing factors for the progression to chronic epilepsy. Methods: A total of 84 patients diagnosed with antibody-mediated AE at The First Affiliated Hospital of Dalian Medical University from January 2016 to December 2024 were included. The data collected encompassed society demographic information, clinical manifestations, long-term video-electroencephalography (LT-VEEG), MRI, treatment and prognostic outcomes. Univariate and multivariate stepwise Logistic regression analyses were conducted to identify influencing factors for the progression from acute symptomatic seizures to chronic epilepsy. Furthermore, the receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to determine the predictive efficacy of the influencing factors Results: 1) The incidence of acute symptomatic seizures in antibody-mediated AE by different antibody subtypes was 85.71% (72/84). The primary seizure types were generalized tonic-clonic seizures (GTCS; 72.22%, 52/72), focal impaired consciousness seizure (FIC; 51.39%, 37/72), focal preserved consciousness seizure (FPC; 41.67%, 30/72), and focal to bilateral tonic-clonic seizure (FBTCS; 43.06%, 31/72), with status epilepticus (SE; 29.17%, 21/72) and subclinical electrical seizures (8.33%, 6/72) were also frequently observed. Among them, the acute symptomatic seizures in anti-leucine-rich glioma-inactivated 1 (LGI1) antibody-associated encephalitis (n = 35) manifested as mesial temporal lobe epilepsy (mTLE)-like seizures, faciobrachial dystonic seizures (FBDS), or both. In anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (n = 16) and anti-myelin oligodendrocyte glycoprotein (MOG) antibody encephalitis (n = 5), acute symptomatic seizures were primarily GTCS, often accompanied by focal seizures of neocortical origin, and were prone to SE. In anti-γ-aminobutyric acid receptor type B (GABA_BR, n = 12) antibody-associated encephalitis and anti-glutamic acid decarboxylase 65 (GAD65) antibody-associated encephalitis (n = 10), acute symptomatic seizures often presented as mTLE-like seizures. 2) Of the 72 patients with acute symptomatic seizures, 23 (31.94%) developed chronic epilepsy; among them, anti-GAD65 and anti-GABA_BR antibody-associated encephalitis had the highest proportions (8/ 8 and 8/12, respectively). 3) Logistic regression analysis showed limbic system atrophy was identified as risk factor (OR = 24.985, 95%CI: 2.873-217.304; P = 0.004), while a normal blood neutrophil count was protective factor (OR = 0.172, 95%CI: 0.038-0.786; P = 0.023) for the progression from acute symptomatic seizures to chronic epilepsy. ROC curve showed that the AUC of limbic system atrophy and normal blood neutrophil count were 0.654 and 0.638, respectively. The AUC of the combined indicator increased to 0.784, indicating improved predictive efficacy (Z = 2.310, P = 0.021; Z = 2.715, P = 0.007). Conclusions: Acute symptomatic seizures in antibody-mediated AE by various subtypes of antibodies exhibit both shared and distinct characteristics. Among them, patients with anti-GAD65 and anti-GABA_BR antibody-associated encephalitis have the highest proportions of developing chronic epilepsy. Limbic system atrophy serves as an independent risk factor, whereas a normal blood neutrophil count acts as an independent protective factor against the progression of acute symptomatic seizures to chronic epilepsy. The combined index has better predictive efficacy.

Key words: Autoimmune diseases of the nervous system, Encephalitis, Autoantibodies, Epilepsy, Risk factors, Logistic models, ROC curve

摘要：

目的: 探讨不同类型抗体介导自身免疫性脑炎的急性症状性癫痫发作临床特点，筛查其转变为慢性癫痫的影响因素。方法: 收集2016年1月至2024年12月于大连医科大学附属第一医院确诊的84例抗体介导自身免疫性脑炎患者，采集社会人口统计学资料及临床表现、长程视频脑电图监测、影像学检查、治疗及预后等临床资料。单因素与多因素逐步法Logistic回归分析筛查抗体介导自身免疫性脑炎急性症状性癫痫发作转变为慢性癫痫的影响因素；绘制受试者工作特征（ROC）曲线并计算曲线下面积，以确定影响因素的预测效能。结果: （1）不同类型抗体介导自身免疫性脑炎急性症状性癫痫发作发生率为85.71%（72/84）。以全面性强直-阵挛发作（72.22%，52/72）、局灶性意识障碍发作（51.39%，37/72）、局灶性意识保留发作（41.67%，30/72）、局灶性进展为双侧强直阵挛发作（43.06%，31/72）为主要发作类型，常出现癫痫持续状态（29.17%，21/72）和临床下电发作（8.33%，6/72）。其中，抗富亮氨酸胶质瘤失活蛋白1抗体相关脑炎（35例）的急性症状性癫痫发作表现为内侧颞叶癫痫样发作、面-臂肌张力障碍发作或二者兼而有之；抗N-甲基-D-天冬氨酸受体脑炎（16例）和抗髓鞘少突胶质细胞糖蛋白抗体脑炎（5例）以全面性强直-阵挛发作为主，常伴新皮质起源的局灶性发作，易出现癫痫持续状态；抗γ-氨基丁酸B型受体（GABA_BR）抗体相关脑炎（12例）和抗谷氨酸脱羧酶65（GAD65）抗体相关脑炎（10例）常表现为内侧颞叶癫痫样发作。（2）72例表现为急性症状性癫痫发作患者中23例（31.94%）转变为慢性癫痫，其中抗GAD65抗体相关脑炎和抗GABA_BR抗体相关脑炎比例最高（分别为8/8和8/12）。（3）Logistic回归分析显示，边缘系统萎缩是急性症状性癫痫发作转变为慢性癫痫的危险因素（OR =24.985，95% CI：2.873~217.304；P=0.004），血常规中性粒细胞计数正常是保护因素（OR =0.172，95% CI：0.038~0.786；P=0.023）。ROC曲线显示，边缘系统萎缩的曲线下面积为0.654，中性粒细胞计数正常为0.638，二者联合的曲线下面积提升至0.784，二者联合具有更好的预测效能（Z =2.310，P=0.021；Z =2.715，P=0.007）。结论: 不同类型抗体介导自身免疫性脑炎的急性症状性癫痫发作既有共性又有各自特点。抗GAD65抗体相关脑炎和抗GABA_BR抗体相关脑炎的急性症状性癫痫发作转变为慢性癫痫的比例高于其他抗体介导自身免疫性脑炎。边缘系统萎缩是不同类型抗体介导自身免疫性脑炎急性症状性癫痫发作转变为慢性癫痫的危险因素，血常规中性粒细胞计数正常是保护因素，二者联合具有更好的预测效能。

关键词: 神经系统自身免疫疾病, 脑炎, 自身抗体, 癫痫, 危险因素, Logistic模型, ROC曲线