Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Mar 28;48(3):386-396. doi: 10.11817/j.issn.1672-7347.2023.220548.
Autoimmune encephalitis arising from autoantibodies against leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) are rare and with high clinical heterogeneity. They are easily misdiagnosed and missing diagnosed. This study aims to explore the clinical characteristics, auxiliary examinations, therapies and prognosis of anti-LGI1 and anti-CASPR2 encephalitis.
Seventeen anti-LGI1 and 11 anti-CASPR2 encephalitis patients who were admitted to the Department of Neurology, Xiangya Hospital, Central South University between January 2018 and January 2021 were collected and retrospectively analyzed. Autoimmune encephalitis related antibodies and paraneoplastic antibodies were screened in all patients. The clinical manifestations, results of laboratory tests, imaging features, treatments and outcomes of 2 encephalitis groups were analyzed and compared.
In the anti-LGI1 encephalitis group, the age of 17 patients was 28-83 (53.18±19.08) years old, and the ratio of male to female was 9꞉8. There were 10 patients with cognitive impairment, 7 seizures, 4 faciobrachial dystonic seizures, and 1 psychiatric disturbance. Hyponatremia was observed in 7 patients. Eight patients had increased slow waves and 5 had epileptic discharge in electroencephalogram (EEG). Brain magnetic resonance (MRI) showed T-weighted imaging (TWI) and fluid attenuated inversion recovery (FLAIR) hyperintense signal in the temporal lobe, hippocampus and basal ganglia in 13 patients. In the anti-CASPR2 group, the age of 11 patients was 17-68 (47.18±16.20) years old, and the ratio of male to female was 5꞉6, with 7 limbic encephalitis, 1 Morvan syndrome, and 3 acquired neuromyotonia (NMT). Three patients had increased slow waves and 2 had epileptic discharge in EEG. Brain MRI showed TWI and FLAIR hyperintense signal in the temporal lobe, hippocampus in 2 patients. Steroids, intravenous immunoglobin, and plasma exchange were administrated in 16 anti-LGI1 encephalitis and 8 anti-CASPR2 encephalitis patients with good therapeutic responses. Among them, 1 patient with anti-LGI1 encephalitis and 3 with anti-CASPR2 encephalitis were administrated with mycophenolate mofetil for immune maintenance therapy. No recurrences were observed in all patients with immunotherapy except for 2 patients who lost of follow-up. There were significant differences in cognitive impairment, hyponatremia, and brain MRI abnormalities between anti-LGI1 and anti-CASPR2 encephalitis patients (all <0.05).
Limbic encephalitis is a common syndrome in both anti-LGI1 and anti-CASPR2 encephalitis patients. Anti-CASPR2 encephalitis has a wider clinical spectrum than anti-LGI1 encephalitis, presenting as NMT and Morvan syndrome, which has a closer relationship with tumors. Both of these 2 antibodies associated disorders are sensitive to immunotherapy and have a good prognosis.
抗富亮氨酸胶质瘤失活蛋白 1（LGI1）和接触蛋白相关蛋白样 2（CASPR2）自身抗体引起的自身免疫性脑炎罕见且具有高度临床异质性。它们很容易被误诊和漏诊。本研究旨在探讨抗 LGI1 和抗 CASPR2 脑炎的临床特征、辅助检查、治疗和预后。
收集 2018 年 1 月至 2021 年 1 月期间在中南大学湘雅医院神经内科住院的 17 例抗 LGI1 脑炎和 11 例抗 CASPR2 脑炎患者，并进行回顾性分析。所有患者均筛查自身免疫性脑炎相关抗体和副肿瘤抗体。分析比较两组脑炎患者的临床表现、实验室检查结果、影像学特征、治疗及转归。
在抗 LGI1 脑炎组中，17 例患者的年龄为 28-83（53.18±19.08）岁，男女比例为 9：8。其中 10 例患者有认知障碍，7 例有癫痫发作，4 例有面臂肌张力障碍发作，1 例有精神障碍。7 例患者存在低钠血症。8 例患者脑电图（EEG）显示有慢波增多，5 例有癫痫样放电。脑磁共振成像（MRI）显示 13 例患者颞叶、海马和基底节区 T 加权成像（TWI）和液体衰减反转恢复（FLAIR）高信号。在抗 CASPR2 组中，11 例患者的年龄为 17-68（47.18±16.20）岁，男女比例为 5：6，其中 7 例为边缘性脑炎，1 例为莫旺综合征，3 例为获得性肌强直（NMT）。3 例患者脑电图显示有慢波增多，2 例有癫痫样放电。脑 MRI 显示 2 例患者颞叶、海马区 TWI 和 FLAIR 高信号。16 例抗 LGI1 脑炎和 8 例抗 CASPR2 脑炎患者接受了类固醇、静脉注射免疫球蛋白和血浆置换治疗，均取得了良好的治疗反应。其中，1 例抗 LGI1 脑炎和 3 例抗 CASPR2 脑炎患者接受了霉酚酸酯进行免疫维持治疗。除 2 例失访患者外，所有接受免疫治疗的患者均未复发。抗 LGI1 脑炎和抗 CASPR2 脑炎患者在认知障碍、低钠血症和脑 MRI 异常方面存在显著差异（均<0.05）。
边缘性脑炎是抗 LGI1 和抗 CASPR2 脑炎患者的常见综合征。抗 CASPR2 脑炎的临床谱比抗 LGI1 脑炎更广，表现为 NMT 和莫旺综合征，与肿瘤的关系更为密切。这两种与抗体相关的疾病对免疫治疗均敏感，预后良好。
