Anti-seizure related 6 homolog like 2 antibody-associated encephalitis: two cases report and literature review

doi:10.3969/j.issn.1672-6731.2025.12.008

Abstract

Abstract:

Objective: To report and analyze clinical features of anti-seizure related 6 homolog like 2 (SEZ6L2) antibody-associated encephalitis, and review relevant literatures. Methods and Results: Two patients were all diagnosed and treated by Ruijin Hospital, Shanghai Jiaotong University School of Medicine from January 2022 to July 2024. The clinical manifestations were mainly with ataxia, gait abnormalities, cognitive dysfunction and bradykinesia. One case exhibited dysautonomia. Cerebrospinal fluid (CSF) white cell counts were elevated, and both serum and CSF antibodies related to autoimmune encephalitis were negative. Further testing for anti-SEZ6L2 antibody revealed that CSF and (or) serum were positive. MRI showed cerebellar atrophy, while ¹⁸F-DPA714 PET/MRI indicated abnormal increased uptake in the cerebellum. ¹⁸F-FDG PET did not reveal any malignant tumors, however, one case showed decreased metabolism in the cerebellum, frontal lobe and temporal lobe. The clinical diagnosis was anti-SEZ6L2 antibody-associated encephalitis, and after immunotherapy, the symptoms improved. Conclusions: Anti-SEZ6L2 antibody-associated encephalitis is rare, and it has complicated clinical manifestations. There are difficulties in the early diagnosis and differential diagnosis, but early immunomodulatory treatment leads to a good prognosis in some patients.

Key words: Encephalitis, Autoimmune diseases, Autoantibodies, SEZ6L2(not in MeSH)

摘要：

目的: 报告2例抗癫痫相关蛋白6同源物2（SEZ6L2）抗体相关脑炎病例，通过复习相关文献，总结抗SEZ6L2抗体相关脑炎临床特征。方法与结果: 纳入2022年1月至2024年7月上海交通大学医学院附属瑞金医院诊断与治疗的2例抗SEZ6L2抗体相关脑炎患者。2例患者临床主要表现为共济失调、步态异常、认知功能障碍、运动迟缓，其中1例存在自主神经功能障碍；脑脊液白细胞计数增加，血清和脑脊液自身免疫性脑炎相关抗体阴性，进一步检测抗SEZ6L2抗体，血清和（或）脑脊液均阳性；头部MRI显示小脑萎缩，¹⁸F-DPA714 PET/MRI显示小脑摄取异常增高，提示神经炎症；¹⁸F-FDG PET未见恶性肿瘤，其中1例显示小脑、额叶和颞叶代谢降低。临床诊断为抗SEZ6L2抗体相关脑炎，经免疫治疗后症状好转。结论: 抗SEZ6L2抗体相关脑炎罕见，临床表现复杂多样，早期诊断与鉴别诊断困难，早期予免疫调节治疗对预后至关重要。

关键词: 脑炎, 自身免疫疾病, 自身抗体, 癫痫相关蛋白6同源物2（非MeSH词）

Na CHENG, Yi-zhou LU, Sheng CHEN, Qin-ming ZHOU. Anti-seizure related 6 homolog like 2 antibody-associated encephalitis: two cases report and literature review[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2025, 25(12): 1150-1156.

程娜, 卢逸舟, 陈晟, 周勤明. 抗癫痫相关蛋白6同源物2抗体相关脑炎两例并文献复习[J]. 中国现代神经疾病杂志, 2025, 25(12): 1150-1156.

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URL: https://journal11.magtechjournal.com/cjcnn/EN/10.3969/j.issn.1672-6731.2025.12.008

https://journal11.magtechjournal.com/cjcnn/EN/Y2025/V25/I12/1150

Figures/Tables 3

References 28

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序号	文献来源	性别	年龄（岁）	免疫相关合并症	临床症状与体征	脑脊液检查	影像学检查	治疗	转归
1	Yaguchi等^[10] (2014)	女性	60	无	共济失调，视网膜病变	正常	头部MRI正常(2年后小脑萎缩)；未检出肿瘤	免疫治疗(具体不详)	好转；随访21个月复发
2	Bonche等^[14] (2019)	女性	55	克罗恩病	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；PET/CT正常；未检出肿瘤	ⅣIg，利妥昔单抗	好转；随访12个月复发
3	Landa等^[15] (2020)	男性	69	无	构音障碍，共济失调，运动迟缓	淋巴细胞计数增多(90×10⁶/L)	头部MRI正常；PET/CT正常；未检出肿瘤	甲泼尼龙，ⅣIg，利妥昔单抗，环磷酰胺	逐渐加重；随访16个月时mRS评分4分
4	Landa等^[16] (2020)	女性	55	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩卵巢癌(发病4年后)	甲泼尼龙，ⅣIg	逐渐加重；随访52个月后死亡
5	Landa等^[18] (2020)	男性	54	膜性肾病	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；未检出肿瘤	甲泼尼龙，血浆置换	逐渐加重；随访36个月时mRS评分3分
6	Landa等^[19] (2020)	女性	69	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；未检出肿瘤	泼尼松，环磷酰胺	逐渐加重；随访72个月时mRS评分4分
7	Reis-Cameron等^[16] (2022)	女性	62	甲状腺功能减退症	共济失调，步态异常	蛋白定量升高(870mg/L)，白蛋白(2130pg/ml)	头部MRI增强扫描显示海马萎缩，右侧海马长T2信号；PET/CT疑诊肿瘤(经穿刺活检证实为小细胞肿瘤)	甲泼尼龙，ⅣIg，肺癌化疗	逐渐加重；随访5个月后死亡
8	Mehdiyeva等^[17] (2022)	女性	73	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；PET/CT正常；未检出肿瘤	甲泼尼龙，ⅣIg，利妥昔单抗，环磷酰胺	好转；随访15个月复发
9	Kather等^[18] (2022)	女性	70	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；PET/CT显示乳腺癌	ⅣIg，利妥昔单抗，放化疗	好转；随访15个月复发
10	Abe等^[19] (2023)	男性	> 50~60	无	构音障碍，共济失调	正常	头部MRI正常；SPECT显示小脑血流量减少；未检出肿瘤	甲泼尼龙，ⅣIg，血浆置换	逐渐加重；随访时间不详
11	Abe等^[19] (2023)	男性	> 60~70	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；未检出肿瘤	甲泼尼龙，ⅣIg，血浆置换	逐渐加重；随访时间不详
12	Matsuyama等^[20] (2023)	男性	35	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；PET/CT正常；未检出肿瘤	甲泼尼龙，ⅣIg，血浆置换	好转；随访12个月复发
13	本文例1	女性	67	糖尿病	构音障碍，共济失调，自主神经功能障碍	蛋白定量异常增高	头部MRI显示小脑萎缩；PET/CT正常；未检出肿瘤	甲泼尼龙，ⅣIg，血浆置换，利妥昔单抗	好转；随访15个月复发
14	本文例2	女性	50	无	构音障碍，共济失调，运动迟缓	白细胞计数轻度增多(26×10⁶/L)	头部MRI显示小脑萎缩；PET/CT正常；未检出肿瘤	甲泼尼龙，ⅣIg，血浆置换，环磷酰胺	好转；随访2个月复发

序号	文献来源	性别	年龄（岁）	免疫相关合并症	临床症状与体征	脑脊液检查	影像学检查	治疗	转归
1	Yaguchi等^[10] (2014)	女性	60	无	共济失调，视网膜病变	正常	头部MRI正常(2年后小脑萎缩)；未检出肿瘤	免疫治疗(具体不详)	好转；随访21个月复发
2	Bonche等^[14] (2019)	女性	55	克罗恩病	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；PET/CT正常；未检出肿瘤	ⅣIg，利妥昔单抗	好转；随访12个月复发
3	Landa等^[15] (2020)	男性	69	无	构音障碍，共济失调，运动迟缓	淋巴细胞计数增多(90×10⁶/L)	头部MRI正常；PET/CT正常；未检出肿瘤	甲泼尼龙，ⅣIg，利妥昔单抗，环磷酰胺	逐渐加重；随访16个月时mRS评分4分
4	Landa等^[16] (2020)	女性	55	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩卵巢癌(发病4年后)	甲泼尼龙，ⅣIg	逐渐加重；随访52个月后死亡
5	Landa等^[18] (2020)	男性	54	膜性肾病	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；未检出肿瘤	甲泼尼龙，血浆置换	逐渐加重；随访36个月时mRS评分3分
6	Landa等^[19] (2020)	女性	69	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；未检出肿瘤	泼尼松，环磷酰胺	逐渐加重；随访72个月时mRS评分4分
7	Reis-Cameron等^[16] (2022)	女性	62	甲状腺功能减退症	共济失调，步态异常	蛋白定量升高(870mg/L)，白蛋白(2130pg/ml)	头部MRI增强扫描显示海马萎缩，右侧海马长T2信号；PET/CT疑诊肿瘤(经穿刺活检证实为小细胞肿瘤)	甲泼尼龙，ⅣIg，肺癌化疗	逐渐加重；随访5个月后死亡
8	Mehdiyeva等^[17] (2022)	女性	73	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；PET/CT正常；未检出肿瘤	甲泼尼龙，ⅣIg，利妥昔单抗，环磷酰胺	好转；随访15个月复发
9	Kather等^[18] (2022)	女性	70	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；PET/CT显示乳腺癌	ⅣIg，利妥昔单抗，放化疗	好转；随访15个月复发
10	Abe等^[19] (2023)	男性	> 50~60	无	构音障碍，共济失调	正常	头部MRI正常；SPECT显示小脑血流量减少；未检出肿瘤	甲泼尼龙，ⅣIg，血浆置换	逐渐加重；随访时间不详
11	Abe等^[19] (2023)	男性	> 60~70	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；未检出肿瘤	甲泼尼龙，ⅣIg，血浆置换	逐渐加重；随访时间不详
12	Matsuyama等^[20] (2023)	男性	35	无	构音障碍，共济失调	正常	头部MRI显示小脑萎缩；PET/CT正常；未检出肿瘤	甲泼尼龙，ⅣIg，血浆置换	好转；随访12个月复发
13	本文例1	女性	67	糖尿病	构音障碍，共济失调，自主神经功能障碍	蛋白定量异常增高	头部MRI显示小脑萎缩；PET/CT正常；未检出肿瘤	甲泼尼龙，ⅣIg，血浆置换，利妥昔单抗	好转；随访15个月复发
14	本文例2	女性	50	无	构音障碍，共济失调，运动迟缓	白细胞计数轻度增多(26×10⁶/L)	头部MRI显示小脑萎缩；PET/CT正常；未检出肿瘤	甲泼尼龙，ⅣIg，血浆置换，环磷酰胺	好转；随访2个月复发

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