边缘性脑炎综合征患者中筛查出的自身免疫性脑炎和病毒性脑炎临床特征比较

Comparison of clinical features of autoimmune encephalitis with viral encephalitis in patients with limbic encephalitis syndrome

目的研究边缘性脑炎（limbic encephalitis，LE）综合征患者中确诊为自身免疫性脑炎（autoimmune encephalitis，AE）的比例，并比较AE与病毒性脑炎的临床特征。方法对2015年12月至2016年6月于华山医院神经内科诊断为LE综合征患者的脑脊液和血清进行AE相关抗体（抗N－甲基－D－天冬氨酸受体抗体、抗α－氨基－3－羟基－5－甲基－4－异唑丙酸受体抗体、抗γ－氨基丁酸B受体抗体、抗富亮氨酸胶质瘤失活蛋白1抗体和抗接触素相关蛋白2抗体）检测，同时收集患者的临床和辅助检查资料进行回顾性分析。结果共有54例患者诊断为LE综合征，其中男性35例，女性19例，年龄15～75岁，平均年龄（38.98±17.29）岁。其中20例（37.0%）为AE相关抗体阳性患者，17例（31.5%）为病毒性脑炎，其他包括3例（5.6%）神经梅毒，1例（1.9%）胶质瘤和13例（24.1%）不明病因患者。青少年（15～29岁）和中老年（≥ 45岁）患者分别占AE和病毒性脑炎总病例数的46.0%（17/37）和37.8%（14/37）。AE组的疾病平均发生时间长于病毒性脑炎组[分别为（22.45±11.62）与（6.24±2.95） d，t＝6.015，P〈0.01]。AE组通过急诊入院的比例低于病毒性脑炎组（3/20与12/17，P＝0.001）。AE组起病时有发热症状的比例、以癫痫为神经系统首发症状的比例低于病毒性脑炎组（8/20与15/17，P＝0.006；2/20与8/17，P＝0.023）。AE组脑脊液白细胞计数异常比例低于病毒性脑炎组（7/17与12/15，P＝0.036）。但两组患者的年龄、性别比例、疾病严重程度及头颅MRI、脑电图、脑脊液蛋白异常率的差异均无统计学意义（均P〉0.05）。肿瘤筛查发现AE患者中有6例（6/19）合并肿瘤。结论AE在LE综合征中并不少见，对LE综合征患者进行AE相关抗体筛查是有价值的。AE与病毒性脑炎各有特征，识别这些特征有助于二者的鉴别诊断及有效干预。

ObjectiveTo investigate the frequency of autoimmune encephalitis （AE） in limbic encephalitis （LE） syndrome and compare its clinical features with viral encephalitis.MethodsPatients diagnosed with LE syndrome who admitted to Huashan Hospital between December 2015 and June 2016 were enrolled and screened for autoantibodies associated with AE （anti-N-methyl-D-aspartate receptor, anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, anti-gamma-amino-butyric acid B-receptor, anti-leucine-rich glioma inactivated 1 and anti-contactin-associated protein-like 2 antibodies） in cerebrospinal fluid （CSF） and serum. Their clinical features and auxiliary examinations were also collected and analyzed retrospectively.ResultsFifty-four patients were diagnosed with LE syndrome, including 35 males and 19 females. The age of these patients was （38.98±17.29） （15-75） years. Twenty patients （37.0%） were identified as AE, 17 patients （31.5%） as viral encephalitis. Other cases included three （5.5%） with neurosyphilis, one （1.9%） with glioma and 13 （24.1%） of unknown cause. Young patients（15-29 years old）and patients older than 45 years accounted for 46.0% （17/37） and 37.8% （14/37） of all AE and viral encephalitis cases respectively. Patients with AE had longer disease progression time than patients with viral encephalitis （（22.45±11.62） d vs （6.24±2.95） d, t=6.015, P〈0.01）. Emergency hospitalization of patients with AE was less frequent than that of patients with viral encephalitis （3/20 vs 12/17, P=0.001）. Patients with AE were less common to present with fever at disease onset than patients with viral encephalitis （8/20 vs 15/17, P=0.006）. Seizures as the first neurological symptom were less common in AE than in viral encephalitis （2/20 vs 8/17, P=0.023）. White blood cell counts in CSF were less frequently elevated in AE than in viral encephalitis （7/17 vs 12/15, P=0.036）. The differences of age, gender, disease severity as well as abnormal rates of brain MRI, electroencephalogram and CSF protein were not statistically significant between the two groups. Tumors were discovered in 6 （6/19） patients with AE.ConclusionsThe frequency of AE in LE syndrome is not low. It is worthwhile to screen for autoantibodies associated with AE in patients diagnosed with LE syndrome. AE and viral encephalitis have their own characteristics, which could offer help in differential diagnosis between them and application of effective treatment.