以抽动障碍为首发症状的抗DPPX抗体相关性自身免疫性脑炎1例报告

doi:10.12372/jcp.2025.24e0231

摘要/Abstract

摘要：

回顾性分析1例以抽动表现起病，后出现明显的精神行为异常、尿频的抗二肽基肽酶样蛋白-6（DPPX）相关自身免疫性脑炎患儿的病历资料，并复习既往发表的抗DPPX相关自身免疫性脑炎的相关文献。探讨以抽动障碍为首发症状的抗DPPX相关性自身免疫性脑炎的临床特点及预后，提高儿科医师对该疾病的认识。患儿女，7岁，因明显的抽动表现入院，逐渐出现精神行为异常及尿频表现。头颅磁共振平扫基本正常；脑电图提示背景节律慢化；血清和脑脊液中抗DPPX抗体滴度升高（血清滴度1∶32，脑脊液滴度1∶1），肿瘤相关筛查未见异常。经免疫治疗后症状明显缓解，随访15个月未复发。检索并总结共37篇文献，总计报道了88例抗DPPX相关自身免疫性脑炎，以抽动障碍为首发症状的尚未报道。儿童抗DPPX相关性自身免疫性脑炎以抽动障碍为首发症状罕见，本例免疫治疗后效果好。临床医师须意识到该疾病的异质性，谨防漏诊。

关键词: 抽动障碍, DPPX抗体, 精神行为异常, 尿频, 自身免疫性脑炎

Abstract:

A retrospective analysis was performed on the clinical data of a 7-year-old girl with anti-DPPX antibody-associated autoimmune encephalitis who initially presented with tic-like symptoms and subsequently developed significant behavioral abnormalities and frequent urination. This case was reviewed in conjunction with previously published literature on anti-DPPX-related autoimmune encephalitis to investigate the clinical features and prognosis of this condition when tic disorders are the initial symptom, hereby enhancing pediatricians' awareness of this rare presentation. The patient was admitted due to prominent tic-like symptoms and progressively exhibited behavioral abnormalities and frequent urination. Brain MRI showed no significant abnormalities, while EEG demonstrated a slowed background rhythm. Elevated titers of anti-DPPX antibodies were detected in both serum (1∶32) and cerebrospinal fluid (1∶1), and tumor-related screening revealed no abnormalities. Following immunotherapy, her symptoms significantly improved, and no recurrence was observed during the 15-month follow-up period. A total of 37 articles were reviewed, summarizing 88 cases of anti-DPPX-related autoimmune encephalitis. However, no cases presenting with tic disorders as the initial symptom have been reported. Anti-DPPX antibody-associated autoimmune encephalitis presenting with tic disorders as the initial symptom is exceedingly rare in children. In this case, immunotherapy yielded favorable results. Clinicists should be vigilant regarding the heterogeneity of this disease to avoid missed or delayed diagnoses.

Key words: tic disorders, DPPX antibody, abnormal mental behavior, frequent urination, autoimmune encephalitis

中图分类号:

关秋悦, 谢艺, 陈丽卿, 刘艳. 以抽动障碍为首发症状的抗DPPX抗体相关性自身免疫性脑炎1例报告[J]. 临床儿科杂志, 2025, 43(8): 621-627.

GUAN Qiuyue, XIE Yi, CHEN Liqing, LIU Yan. Anti-DPPX antibody-associated autoimmune encephalitis with tic disorder as the first symptom: a case report[J]. Journal of Clinical Pediatrics, 2025, 43(8): 621-627.

图/表 4

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表1

7例≤18岁抗DPPX抗体脑炎患者的基线特征、治疗及预后"

患者	性别	发病年龄/岁	主要临床表现	头颅影像	EEG	抗体	治疗及预后
1^[24]	男	15	认知障碍、共济失调、肌强直、眼震颤、过度惊跳、反射亢进	头颅MRI、FDG-PET显像无异常	无异常	脑脊液抗DPPX抗体1∶320；血清抗DPPX抗体1∶10000	甲基泼尼松龙、免疫球蛋白、血浆置换未改善病情或短暂减轻症状，症状复发后42个月开始使用利妥昔单抗，效果良好
2^[6]	女	13	恶心等消化道症状、发作性共济失调、复视、眼肌麻痹、睡眠障碍	未报道	未报道	血清抗DPPX抗体阳性，滴度未报道	甲基泼尼松龙、血浆置换、利妥昔单抗治疗后症状部分缓解，3周后有复发
3^[6]	男	18	呕吐、腹泻、体重减轻等消化道症状、认知障碍、头晕、肌阵挛、眼震颤、复视、尿潴留、癫痫发作	未报道	未报道	血清抗DPPX抗体阳性,滴度未报道	甲基泼尼松龙、硫唑嘌呤，治疗后症状完全改善，随访4年未复发
4^[21]	男	14	认知障碍、精神障碍	头颅MRI无异常	无异常	脑脊液抗DPPX抗体阴性；血清抗DPPX抗体1∶100，抗TPO>600 IU/ml,抗TG 345.03 IU/ml	甲基泼尼松龙、免疫球蛋白治疗后，随访26个月未复发，改良 Rankin 量表评分有改善
5^[21]	男	17	头痛、迁移性肌阵挛	头颅MRI无异常	无异常	脑脊液抗DPPX抗体阴性；血清抗DPPX抗体 1∶100，抗CASPR2 1∶10	甲基泼尼松龙、免疫球蛋白、氯硝西泮和丙戊酸治疗后，患者仍有肌阵挛，进行第二轮免疫球蛋白治疗后，随访2个月未复发，改良 Rankin 量表评分有改善
6^[9]	男	14	便秘、胃轻瘫等消化道症状、认知障碍、反射亢进、肢体麻痹、呼吸衰竭、发热	头颅MRI：脑干、基底神经节和双侧白质中出现广泛的异常信号	未报道	脑脊液抗DPPX抗体阴性；血清抗DPPX抗体1∶320	甲基泼尼松龙、免疫球蛋白治疗后症状改善不完全
7^[27]	男	18	呕吐等消化道症状、头晕、共济失调、眼震颤、发热	头颅MRI无异常	无异常	脑脊液抗DPPX抗体阴性；血清抗DPPX抗体1∶10	甲基泼尼松龙、免疫球蛋白治疗后症状完全改善，1个月内复查血清和脑脊液抗DPPX抗体均为阴性，随访10个月未复发
本例	女	7	头痛、发热、精神行为异常、性格改变、尿频、抽动障碍	头颅MRI：右侧海马较对侧小，右侧侧脑室颞角较对侧大	背景节律慢化，清醒安静闭目状态下双侧枕区见7~ 8 Hz左右θ、α波节律	脑脊液抗DPPX抗体滴度1∶1；血清抗DPPX抗体滴度1∶32	甲基泼尼松龙、免疫球蛋白，治疗后症状完全改善，随访15个月未复发，病程1年复查血清抗DPPX抗体滴度 1:32，病程15个月复查血清抗DPPX抗体滴度1:10

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参考文献 27

[1]	Hara M, Ariño H, Petit-Pedrol M, et al. DPPX antibody-associated encephalitis: main syndrome and antibody effects[J]. Neurology, 2017, 88(14): 1340-1348. doi: 10.1212/WNL.0000000000003796 pmid: 28258082
[2]	Braczkowski M, Soszyński D, Sierakowska A, et al. Autoimmune encephalitis with qntibodies: qnti-NMDAR, qnti-AMPAR, qnti-GQ1b, qnti-DPPX, qnti-CASPR2, qnti-LGI1, qnti-RI, qnti-Yo, qnti-Hu, qnti-CV2 and qnti-GABAAR, in the course of psychoses, neoplastic diseases, and paraneoplastic syndromes[J]. Diagnostics (Basel), 2023, 13(15): 2589.
[3]	Boronat A, Gelfand JM, Gresa-Arribas N, et al. Encephalitis and antibodies to dipeptidyl-peptidase-like protein-6, a subunit of Kv4.2 potassium channels[J]. Ann Neurol, 2013, 73(1): 120-128. doi: 10.1002/ana.23756 pmid: 23225603
[4]	Sun W, Maffie JK, Lin L, et al. DPP6 establishes the A-type K(+) current gradient critical for the regulation of dendritic excitability in CA1 hippocampal neurons[J]. Neuron, 2011, 71(6): 1102-1115. doi: 10.1016/j.neuron.2011.08.008 pmid: 21943606
[5]	周勤明, 蔡勇, 倪优, et al. 抗二肽基肽酶样蛋白-6抗体脑炎[J]. 中国现代神经疾病杂志, 2020, 20(10): 862-7. doi: 10.3969/j.issn.1672-6731.2020.10.004
	Zhou QM, Cai Y, Ni Y, et al. Anti-dipeptidyl-peptidase-like protein 6 antibody encephalitis[J]. Zhongguo Xiandai Shenjing Jibing Zazhi, 2020, 20(10): 862-867.
[6]	Tobin WO, Lennon VA, Komorowski L, et al. DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients[J]. Neurology, 2014, 83(20): 1797-1803. doi: 10.1212/WNL.0000000000000991 pmid: 25320100
[7]	理二闯, 章殷希, 丁美萍. 二肽基肽酶样蛋白-6抗体相关脑炎临床诊治进展[J]. 中华神经科杂志, 2021, 54(4): 424-428.
	Li EC, Zhang YX, Ding MP. Clinical advances in diagnosis and treatment of anti-dipeptidyl-peptidase-like protein 6 antibody-associated encephalitis[J]. Zhonghua Shenjingke Zazhi, 2021, 54(4): 424-428.
[8]	Wijntjes J, Bechakra M, Schreurs MWJ, et al. Pruritus in anti-DPPX encephalitis[J]. Neurol Neuroimmunol Neuroinflamm, 2018, 5(3): e455.
[9]	Xiao J, Fu PC, Li ZJ. Clinical and imaging analysis to evaluate the response of patients with anti-DPPX encephalitis to immunotherapy[J]. BMC Neurol, 2022, 22(1): 129.
[10]	Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis[J]. Lancet Neurol, 2016, 15(4): 391-404. doi: 10.1016/S1474-4422(15)00401-9 pmid: 26906964
[11]	Cellucci T, Van Mater H, Graus F, et al. Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient[J]. Neurol Neuroimmunol Neuroinflamm, 2020, 7(2): e663.
[12]	Bjerknes TL, Steihaug OM, Haugen M, et al. Case report: pain in anti-DPPX encephalitis[J]. Front Neurol, 2022, 13: 1091688.
[13]	Bressers AA, Goto NA, Piepers S, et al. Autoimmune encephalitis due to mantle cell lymphoma[J]. Ned Tijdschr Geneeskd, 2016, 160: D394. pmid: 27758720
[14]	欧阳丽君, 贺莹, 陈晓岗. 误诊为躯体形式障碍的DPPX相关自身免疫性脑炎1例[J]. 中国神经精神疾病杂志, 2020, 46(02): 110-112.
	Ouyang LJ, He Y, Chen XG. A case of anti-DPPX autoimmune encephalitis misdiagnosed as somatic symptom disorder[J]. Zhongguo Shenjing Jingshen Jibing Zazhi, 2020, 46(2): 110-112.
[15]	张炜华, 邹丽萍, 任海涛, 等. 警惕儿童自身免疫性脑炎诊治陷阱[J]. 临床儿科杂志, 2023, 41(9): 644-649.
	Zhang WH, Zou LP, Ren HT, et al. Beware of the pitfalls in diagnosis and treatment of autoimmune encephalitis in children[J]. Linchuang Erke Zazhi, 2023, 41(9): 644-649.
[16]	陈燕惠, 林桂秀, 林秋君, 等. 儿童抽动障碍与微小病毒B_(19)感染和免疫功能[J]. 中国心理卫生杂志, 2006, (4): 218-220.
	Chen YH, Lin GX, Lin QJ, et al. Tic disorders in children and their association with parvovirus B19 infection and immune function[J]. Zhongguo Xinli Weisheng Zazhi, 2006(4):218-220.
[17]	郭徵艺, 阳柯佳, 雷静, 等. 中国儿童抽动障碍预后影响因素的系统评价[J]. 中国中西医结合儿科学, 2023, 15(4): 283-290.
	Guo ZY, Yang KJ, Lei J, et al. Systematic review of prognostic factors for tic disorders in Chinese children[J]. Zhongguo Zhongxiyi Jiehe Erkexue, 2023, 15(4): 283-290.
[18]	匡桂芳, 贺莉娜, 邓萍. 巨细胞病毒感染在抽动障碍中的临床意义初探[J]. 中国心理卫生杂志, 2001, (3): 201-202.
	Kuang GF, He LN, Deng P. Preliminary study on the clinical significance of cytomegalovirus infection in tic disorders[J]. Zhongguo Xinli Weisheng Zazhi, 2001, (3): 201-202.
[19]	Snider LA, Swedo SE. PANDAS: current status and directions for research[J]. Mol Psychiatry, 2004, 9(10): 900-907.
[20]	贾润梅, 图雅, 王育民. 抽动障碍中枢神经递质失衡发病机制的研究进展[J]. 中国医药科学, 2020, 10(21): 45-48.
	Jia RM, Tuya, Wang YM. Research progress on the pathogenesis of neurotransmitter imbalance in tic disorders[J]. Zhongguo Yiyao Kexue, 2020, 10(21): 45-48.
[21]	Miao A, Shi Y, Wang X, et al. Clinical features and prognosis in Chinese patients with dipeptidyl-peptidase-like protein 6 antibody-associated encephalitis[J]. Front Neurol, 2021, 12: 817896.
[22]	王新, 肖洪波. 自身免疫性脑炎14例临床诊治分析[J]. 实用药物与临床, 2021, 24(1): 62-66.
	Wang X, Xiao HB. Clinical analysis of diagnosis and treatment in 14 cases of autoimmune encephalitis[J]. Shiyong Yaowu Yu Linchuang, 2021, 24(1): 62-66.
[23]	Dominguez L, McKeon A, Tobin WO, et al. Long term outcomes in patients with anti-DPPX autoimmunity[J]. J Neuroimmunol, 2023, 384: 578214.
[24]	Balint B, Jarius S, Nagel S, et al. Progressive encephalomyelitis with rigidity and myoclonus: a new variant with DPPX antibodies[J]. Neurology, 2014, 82(17): 1521-1528. doi: 10.1212/WNL.0000000000000372 pmid: 24696508
[25]	Stokin GB, Popović M, Gelpi E, et al. Neuropathologic features of anti-dipeptidyl-peptidase-like protein-6 antibody encephalitis[J]. Neurology, 2015, 84(4): 430-432. doi: 10.1212/WNL.0000000000001183 pmid: 25520315
[26]	张智杰, 徐丹凤, 李玲. 儿童自身免疫性癫痫研究进展[J]. 临床儿科杂志, 2025, 43(5): 395-402.
	Zhang ZJ, Xu DF, LI L. Progress in pediatric autoimmune epilepsy[J]. Linchuang Erke Zazhi, 2025, 43(5): 395-402.
[27]	Lin J, Zhu M, Mao X, et al. Anti-dipeptidyl-peptidase-like protein 6 encephalitis with pure cerebellar ataxia: a case report[J]. BMC Neurol, 2022, 22(1): 242.