Objectives: 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.
Methods: 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.
Results: 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 T2-weighted imaging (T2WI) 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 T2WI 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 P<0.05).
Conclusions: 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.
目的: 抗富亮氨酸胶质瘤失活蛋白1(leucine-rich glioma-inactivated protein 1，LGI1)抗体、抗接触蛋白相关蛋白2(contactin-associated protein-like 2，CASPR2)抗体引起的自身免疫性脑炎较为罕见，临床异质性大，极易漏诊、误诊。本研究旨在总结抗LGI1抗体及抗CASPR2抗体脑炎患者的临床特征。方法: 收集2018年1月至2021年1月中南大学湘雅医院神经内科收治的抗LGI1抗体、抗CASPR2抗体脑炎患者共28例，所有患者进行自身免疫性脑炎相关抗体谱及副肿瘤抗原谱抗体筛查。回顾性分析28例患者的临床表现、辅助检查资料、治疗及随访情况，采用改良Rankin量表评估患者治疗前后的生活能力，并对这2种自身免疫性脑炎的临床特征进行比较和分析。结果: 28例中抗LGI1抗体脑炎17例，发病年龄28~83(53.18±19.08)岁，男女患者之比为9꞉8。临床表现为认知功能障碍的患者有10例，癫痫发作7例，面臂肌张力障碍发作4例，精神行为异常1例。实验室检查发现低钠血症7例；脑脊液检查异常4例，表现为白细胞数或蛋白质含量轻度上升各2例；脑电图异常13例，主要表现为慢波增多(8/13)及痫性放电(5/13)；颅脑磁共振成像(magnetic resonance imaging，MRI)异常13例，主要表现为颞叶、海马及基底节区T2加权成像(T2-weighted imaging，T2WI)及水抑制反转恢复序列(fluid attenuated inversion recovery，FLAIR)呈高信号。抗CASPR2抗体脑炎患者11例，发病年龄17~68(47.18±16.20)岁，男女患者之比为5꞉6。7例为边缘性脑炎，1例为莫旺综合征，3例为获得性神经性肌强直；临床表现为癫痫发作者4例，精神行为异常、认知障碍和意识障碍各1例；脑脊液异常3例，主要表现为白细胞数及蛋白质含量轻度升高；脑电图异常5例，主要表现为慢波增多(3/5)及痫性放电(2/5)；颅脑MRI异常2例，主要表现为颞叶、海马T2WI及FLAIR高信号。16例抗LGI1抗体脑炎及8例抗CASPR2抗体脑炎患者使用糖皮质激素、免疫球蛋白及血浆置换等一线免疫治疗，均反应良好，其中1例抗LGI1抗体脑炎及3例抗CASPR2抗体脑炎患者同时口服吗替麦考酚酯维持治疗；采用免疫治疗的患者除2例失访外，随访期内(6~36个月)均未见明显复发。2种抗体脑炎在认知障碍、低钠血症、颅脑MRI异常上差异均有统计学意义(均P<0.05)。结论: 抗LGI1抗体及抗CASPR2抗体脑炎均可表现为边缘性脑炎，抗LGI1抗体脑炎以认知障碍为主要表现，面臂肌张力障碍发作及低钠血症为特征性表现，易出现颅脑MRI异常；抗CASPR2抗体脑炎以癫痫发作为最常见临床表现，可累及周围神经系统而出现神经性肌强直、莫旺综合征且易合并肿瘤。2种抗体脑炎均对免疫治疗敏感，预后良好。.
Keywords: Morvan syndrome; autoimmune encephalitis; contactin-associated protein-like 2; leucine-rich glioma-inactivated protein 1; neuromyotonia.