抗LGI1脑炎：一项国人单中心队列研究

范思远; 任海涛; 林楠; 卢强; 金丽日; 黄颜; 侯波; 有慧; 冯逢; 崔瑞雪; 朱以诚; 关鸿志; 崔丽英

doi:10.12376/j.issn.2097-0501.2022.02.005

抗LGI1脑炎：一项国人单中心队列研究

doi: 10.12376/j.issn.2097-0501.2022.02.005

1.
中国医学科学院北京协和医院神经科，北京 100730
2.
中国医学科学院北京协和医院放射科，北京 100730
3.
中国医学科学院北京协和医院核医学科，北京 100730

基金项目:

中国医学科学院医学与健康科技创新工程项目 CIFMS 2021-I2M-C&T-A-002

中国医学科学院医学与健康科技创新工程项目 CIFMS 2021-I2M-1-003

详细信息

通信作者:
关鸿志，E-mail：pumchghz@126.com

中图分类号: R74
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出版历程
- 收稿日期: 2022-03-24
- 录用日期: 2022-04-08
- 网络出版日期: 2022-06-02

Anti-Leucine-Rich Glioma-Inactivated 1 Encephalitis: A Single-Center Cohort Study in China

1.
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
2.
Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
3.
Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Funding:

CAMS Innovation Fund for Medical Sciences CIFMS 2021-I2M-C&T-A-002

CAMS Innovation Fund for Medical Sciences CIFMS 2021-I2M-1-003

More Information

Corresponding author: GUANG Hongzhi, Email: pumchghz@126.com

摘要

摘要: 目的抗LGI1脑炎是最常见的自身免疫性边缘性脑炎，本研究拟评估中国抗LGI1脑炎患者的临床特点、免疫治疗方案及长期预后。方法 2013年7月至2018年1月于北京协和医院就诊且存在近事记忆下降、精神症状、癫痫发作、意识障碍等症状，临床怀疑脑炎的患者，进行血清和/或脑脊液抗LGI1抗体检测，纳入抗LGI1抗体阳性的患者。登记入组患者的一般情况、临床表现、辅助检查、免疫治疗、随访与预后等信息，并进行分析。结果共纳入120例患者。66.7%为男性，中位发病年龄为61岁(四分位距：49~66岁)。最常见的首发症状是癫痫发作(65.0%)。95.0%的患者随病情进展出现癫痫发作(其中54.2%出现特征性的面臂肌张力障碍发作)、近事记忆下降(92.5%)和精神行为异常(69.1%)等症状。头磁共振与¹⁸F-FDG PET/CT检查提示病变主要位于单侧或者双侧颞叶内侧，和/或基底节区。95.0%的患者接受静脉注射免疫球蛋白和/或糖皮质激素治疗，47.5%接受吗替麦考酚酯长程免疫治疗，无患者接受血浆置换或二线免疫治疗。中位随访时间为34.2个月(四分位距：22.0~45.6个月)。91.2%的患者预后良好(改良Rankin评分≤2分)。47.8%的患者遗留轻微近事记忆下降。9例患者死亡。发病后首年复发率为24.8%。队列中24例(20%)患者为青年(发病年龄≤45岁)，与中老年患者相比，青年患者中男性更少见(37.5% vs. 74.0%，P＜0.01)，精神行为异常(50.0% vs. 74.0%，P=0.02)、低钠血症(33.3% vs. 68.8%，P＜0.01)和头¹⁸F-FDG PET/CT异常改变(20.8% vs. 47.9%，P=0.02)也更少见，无复发生存概率高于中老年患者。结论抗LGI1脑炎患者以中老年为主，多以典型的边缘性脑炎或者FBDS为主要表现，青年患者可能症状不典型。神经影像学提示边缘系统或者基底节受累。该病患者对免疫治疗反应良好，多数患者预后良好。
- 抗LGI1抗体 /
- 脑炎 /
- 自身免疫 /
- 免疫治疗 /
- 预后
Abstract: Objective To evaluate the clinical and paraclinical features of Chinese patients with anti- LGI1 encephalitis. Methods Patients with memory deficits, psychiatric symptoms, seizures or altered level of consciousness, suspicious of encephalitis, at presentation to Peking Union Medical College Hospital were recruited between July 2013 and January 2018, and tested for anti-LGI1 antibodies in their serum and/or cerebrospinal fluid(CSF) samples. Patients with anti-LGI1 antibodies were enrolled. The demographic characteristics, clinical manifestations, laboratory examination results, neuroimaging features, immunotherapy, follow-up practices and outcomes for included patients were registered and analyzed. Results The study enrolled 120 patients, of whom 66.7% were male. The median age was 61 years (interquartile range [IQR]: 49-66 years). Seizures(65.0%) were the most common initial symptoms. Most patients developed seizures (95.0%), including faciobrachial dystonic seizures (54.2%), memory deficits (92.5%), and psychiatric symptoms (69.1%). Brain MRI and ¹⁸F-FDG PET / CT showed that the lesions were mainly located in unilateral or bilateral medial temporal lobes, and (or) basal ganglia. Of the patients, 95.0% received intravenous immunoglobulin (IVIg) or corticosteroids, 47.5% received mycophenolate mofetil as long-term immunotherapy, and no one received second-line immunotherapy. The median follow-up was 34.2 months(IQR: 22.0-45.6 months). 91.2% had a good outcome (modified Rankin Scale score≤2 points). Residual mild memory deficits were present in 47.8% of the patients. Nine deaths were documented. Relapses occurred in 24.8% of the patients in the first year. In total, 24 (20%)cases were young patients(onset age ≤45 years).There were fewer males among the younger patients(37.5% vs. 74.0%, P < 0.01). Besides, there were fewer younger patients with psychiatric symptoms(50.0% vs. 74.0%, P=0.02), hyponatremia(33.3% vs. 68.8%, P < 0.01), and abnormalities on brain ¹⁸F-FDG PET/CT(20.8% vs. 47.9%, P=0.02). The relapse-free survival rate was significantly higher in the young patients. Conclusions Elderly males were predominant in patients with anti-LGI1 encephalitis. Most patients developed symptoms of limbic encephalitis and/or FDBS during the disease course. Several patients were young adults and lacked typical symptoms. Neuroimaging features were consistent with the involvement of limbic system or basal ganglia. Patients with anti-LGI1 encephalitis respond well to immunotherapy, irrespective of the age.
- anti-LGI1 antibodies /
- encephalitis /
- autoimmune /
- immunotherapy /
- prognosis
注释:

作者贡献：论文选题与设计：关鸿志、范思远; 资料收集：范思远、关鸿志、任海涛、林楠、卢强、金丽日、黄颜、侯波、有慧、冯逢、崔瑞雪; 论文初稿撰写：范思远; 论文整合与修订：范思远、任海涛、林楠、侯波、有慧、冯逢、崔瑞雪、朱以诚、关鸿志、崔丽英; 科研经费来源：关鸿志、范思远。

利益冲突：所有作者均声明不存在利益冲突。

HTML全文

图 1 抗LGI1脑炎患者头¹⁸F-FDG-PET/MRI影像

A、B.患者头¹⁸F-FDG PET/MRI提示右侧颞叶内侧及杏仁核FLAIR高信号病灶; C、D.¹⁸F-FDG高摄取

Figure 1. Brain ¹⁸F-FDG-PET/MRI in a patient with anti-LGI1 encephalitis

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图 2 抗LGI1脑炎患者治疗前后mRS变化

Figure 2. Illustration of modified Rankin Scale(mRS) scores in patients with anti-LGI1 encephalitis at nadir and last follow-up

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图 3 青年(发病年龄≤ 45岁)和中老年(发病年龄＞45岁)抗LGI1脑炎患者无复发生存概率图

Figure 3. Relapse-free survival of younger(onset age≤45- year-old)and elder(onset age > 45-year-old) patients with anti-LGI1 encephalitis

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表 1 120例抗LGI1脑炎患者人口学和临床特点

Table 1. The clinical and demographic features of patients with anti-LGI-1 encephalitis

项目	数值
男性[n(%)]	80 (66.7)
起病年龄[岁，中位数(四分位距，范围)]	61 (49~66，16~96)
≤ 45岁[n(%)]	24(20)
合并症[n(%)]
肿瘤	11(9.2)
其他自身免疫病	8(6.6)
慢性病程[n(%)]	21(17.5)
首发症状
精神行为异常[n(%)]	11(9.2)
近事记忆下降[n(%)]	24(20.0)
癫痫发作[n(%)]	78(65.0)
强直-阵挛发作(n)	27
部分性发作(n)	37
FBDS(n)	14
周围神经系统症状[n(%)]	5(4.2)
睡眠障碍[n(%)]	2(1.7)
临床症状[n(%)]
精神行为异常	83(69.1)
近事记忆下降	111(92.5)
癫痫发作	114(95.0)
FBDS	65(54.2)
频繁发作	86(71.7)
意识水平降低	27(22.5)
睡眠障碍	51(42.5)
病情达峰时状态[n(%)]
症状数量
4个症状	20(16.7)
3个症状	65(54.2)
2个症状	25(20.8)
1个症状	10(8.3)
mRS ≤ 2分	81(67.5)
入住重症监护室	7(5.8)

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表 2 120例抗LGI1脑炎患者实验室检查与神经影像特点

Table 2. The laboratory and neuroimaging features of patients with anti-LGI-1 encephalitis

项目	数值
低钠血症[n(%)]	74(61.7)
其他自身免疫性脑炎相关抗体阳性[n(%)]	8(6.6)
CSF^a
CSF异常[n(%)]	33(28.9)
白细胞计数＞5×10⁶/L[n(%)]	13(11.4)
蛋白水平＞0.45g /L[n(%)]	24(21.0)
CSF特异性寡克隆区带阳性^b[n(%)]	13(19.1)
CSF抗LGI1抗体阳性^c[n(%)]	82(71.9)
神经影像
头MRI异常改变^d[n(%)]	72(61.0)
单侧颞叶内侧受累[n(%)]	35(29.7)
双侧颞叶内侧受累[n(%)]	32(27.1)
基底节区受累[n(%)]	8(6.7)
头¹⁸F-FDG PET/CT异常改变^e[n(%)]	51(87.9)
单侧颞叶内侧受累[n(%)]	22(37.9)
双侧颞叶内侧受累[n(%)]	18(31.0)
基底节区受累[n(%)]	36(62.1)
脑电图异常^f[n(%)]	84(78.5)
n：数量; a.6例患者未接受腰穿; b.52例患者未查脑脊液特异性寡克隆区带; c.6例患者未查脑脊液抗LGI1抗体; d.2例患者未查头MRI; e.62例患者未查头¹⁸F-FDG PET/CT; f.13例患者未查脑电图

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表 3 120例抗LGI1脑炎患者免疫治疗及预后

Table 3. The immunotherapy and prognosis of patients with anti-LGI-1 encephalitis

项目	数值
治疗情况
治疗延迟[周，中位数(四分位距)]	8(4~12.5)
一线免疫治疗[n(%)]	114(95.0)
糖皮质激素[n(%)]	99(82.5)
激素冲击治疗[n(%)]	40(33.3)
糖皮质激素＞3个月[n(%)]	96(80.0)
静脉免疫球蛋白[n(%)]	100(83.3)
血浆置换[n(%)]	0(0)
二线免疫治疗[n(%)]	0(0)
长程免疫抑制剂治疗[n(%)]	60(50.0)
吗替麦考酚酯[n(%)]	57(47.5)
硫唑嘌呤[n(%)]	3(2.5)
随访情况
随访时间[月，中位数(四分位距)]	34.2(22.0~45.6)
失访[n(%)]	7(5.8)
预后情况
复发^a[n(%)]	47(41.6)
仅1次复发(n)	32
共2次复发(n)	13
共3次复发(n)	2
首次复发时间[月，中位数(四分位距)]	12(10~16.3)
预后良好(mRS ≤2分)^b[n(%)]	103(91.2)
死亡^c[n(%)]	9(8.0)
遗留轻微近事记忆下降^d[n(%)]	54(47.8)
病情好转或稳定后持续抗体阳性^e[n(%)]	34(30.1)
a~e: 7例失访患者未计入

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