Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas2Department of Neurology, Parkland Health and Hospital System, Dallas, Texas.
Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas.
JAMA Neurol. 2017 Apr 1;74(4):397-402. doi: 10.1001/jamaneurol.2016.5429.
Autoimmune epilepsy is an underrecognized condition, and its true incidence is unknown. Identifying patients with an underlying autoimmune origin is critical because these patients' condition may remain refractory to conventional antiseizure medications but may respond to immunotherapy.
To determine the prevalence of neurological autoantibodies (Abs) among adult patients with epilepsy of unknown etiology.
DESIGN, SETTING, AND PARTICIPANTS: Consecutive patients presenting to neurology services with new-onset epilepsy or established epilepsy of unknown etiology were identified. Serum samples were tested for autoimmune encephalitis Abs as well as thyroperoxidase (TPO) and glutamic acid decarboxylase 65 (GAD65) Abs. An antibody prevalence in epilepsy (APE) score based on clinical characteristics was assigned prospectively. Data were collected from June 1, 2015, to June 1, 2016.
Presence of neurological Abs. A score based on clinical characteristics was assigned to estimate the probability of seropositivity prior to antibody test results. Good seizure outcome was estimated on the basis of significant reduction of seizure frequency at the first follow-up or seizure freedom.
Of the 127 patients (68 males and 59 females) enrolled in the study, 15 were subsequently excluded after identification of an alternative diagnosis. Serum Abs suggesting a potential autoimmune etiology were detected in 39 (34.8%) cases. More than 1 Ab was detected in 7 patients (6.3%): 3 (2.7%) had TPO-Ab and voltage-gated potassium channel complex (VGKCc) Ab, 2 (1.8%) had GAD65-Ab and VGKCc-Ab, 1 had TPO-Ab and GAD65-Ab, and 1 had anti-Hu Ab and GAD65-Ab. Thirty-two patients (28.6%) had a single Ab marker. Among 112 patients included in the study, 15 (13.4%) had TPO-Ab, 14 (12.5%) had GAD65-Ab, 12 (10.7%) had VGKCc (4 of whom were positive for leucine-rich glioma-inactivated protein 1 [LGI1] Ab), and 4 (3.6%) had N-methyl-D-aspartate receptor (NMDAR) Ab. Even after excluding TPO-Ab and low-titer GAD65-Ab, Abs strongly suggesting an autoimmune cause of epilepsy were seen in 23 patients (20.5%). Certain clinical features, such as autonomic dysfunction, neuropsychiatric changes, viral prodrome, faciobrachial dystonic spells or facial dyskinesias, and mesial temporal sclerosis abnormality on magnetic resonance imaging, correlated with seropositivity. The APE score was a useful tool in predicting positive serologic findings. Patients who were Ab positive were more likely to have good seizure outcome than were patients with epilepsy of unknown etiology (15 of 23 [65.2%] vs 24 of 89 [27.0%]; odds ratio, 4.8; 95% CI, 1.8-12.9; P = .002). In patients who were seropositive, reduction in seizure frequency was associated with use of immunomodulatory therapy.
Among adult patients with epilepsy of unknown etiology, a significant minority had detectable serum Abs suggesting an autoimmune etiology. Certain clinical features (encoded in the APE score) could be used to identify patients with the highest probability of harboring neurological Abs.
自身免疫性癫痫是一种未被充分认识的疾病，其真实发病率尚不清楚。识别潜在自身免疫性病因的患者至关重要，因为这些患者的病情可能对常规抗癫痫药物仍然没有反应，但可能对免疫疗法有反应。
确定成人不明病因癫痫患者中神经自身抗体（Abs）的患病率。
设计、地点和参与者：连续确诊为新发癫痫或不明病因癫痫的患者被确定为研究对象。对血清样本进行自身免疫性脑炎 Abs 以及甲状腺过氧化物酶（TPO）和谷氨酸脱羧酶 65（GAD65）Abs 检测。前瞻性地根据临床特征分配抗体在癫痫中的患病率（APE）评分。数据收集时间为 2015 年 6 月 1 日至 2016 年 6 月 1 日。
存在神经 Abs。根据临床特征分配了一个评分，以在抗体检测结果之前估计血清阳性的概率。根据首次随访时显著减少癫痫发作频率或无癫痫发作来估计良好的癫痫发作结局。
在纳入研究的 127 例患者（68 例男性和 59 例女性）中，15 例在确定替代诊断后被排除在外。在 39 例（34.8%）病例中检测到提示潜在自身免疫病因的血清 Abs。7 例患者（6.3%）检测到超过 1 种 Abs：3 例（2.7%）有 TPO-Ab 和电压门控钾通道复合物（VGKCc）Ab，2 例（1.8%）有 GAD65-Ab 和 VGKCc-Ab，1 例有 TPO-Ab 和 GAD65-Ab，1 例有抗 Hu Ab 和 GAD65-Ab。32 例患者（28.6%）有单一 Abs 标志物。在纳入研究的 112 例患者中，15 例（13.4%）有 TPO-Ab，14 例（12.5%）有 GAD65-Ab，12 例（10.7%）有 VGKCc（其中 4 例对亮氨酸丰富的胶质瘤失活蛋白 1 [LGI1] Ab 呈阳性），4 例（3.6%）有 N-甲基-D-天冬氨酸受体（NMDAR）Ab。即使排除 TPO-Ab 和低滴度 GAD65-Ab，也有 23 例（20.5%）患者的 Abs 强烈提示癫痫的自身免疫原因。某些临床特征，如自主神经功能障碍、神经精神变化、病毒前驱期、面臂肌张力障碍发作或面运动障碍、磁共振成像上的内侧颞叶硬化异常，与血清阳性相关。APE 评分是预测阳性血清发现的有用工具。Abs 阳性的患者比不明病因的癫痫患者更有可能有良好的癫痫发作结局（23 例中的 15 例[65.2%]与 89 例中的 24 例[27.0%]；优势比，4.8；95%CI，1.8-12.9；P = .002）。在血清阳性的患者中，癫痫发作频率的降低与免疫调节治疗的使用相关。
在不明病因的癫痫成人患者中，有相当一部分患者可检测到提示自身免疫性病因的血清 Abs。某些临床特征（编码在 APE 评分中）可用于识别最有可能携带神经 Abs 的患者。
