电压门控钾离子通道复合物抗体及其相关神经综合征

doi:10.3969/j.issn.1004-583X.2021.06.016

摘要/Abstract

摘要：

电压门控钾离子通道复合物抗体(VGKCc抗体)纷繁复杂,本文就VGKCc抗体及其临床意义以及疾病的诊断、鉴别诊断和治疗进行综述。VGKCc抗体中部分抗体具有明确的致病性,如富含亮氨酸的神经胶质瘤灭活蛋白1(LGI1)和接触素相关蛋白2(Casper2)。LGI1 抗体、Casper2 抗体是诊断疾病的重要依据;抗接触蛋白-2(CNTN-2)抗体主要与抗 LGI1 和Caspr2 抗体共存,临床意义相对较小;“双阴抗体”相关的疾病谱广,还需要进一步的研究。VGKCc抗体相关的疾病临床表型多样,主要包括Isaacs综合征、Morvan综合征、边缘叶脑炎、癫痫。LGI1抗体和Caspr2抗体都不是特定神经综合征的病理学表现。在对快速进展性痴呆患者进行诊断时要注意VGKCc抗体相关脑病的可能,要注意与CJD进行鉴别。虽然对于LGI1抗体、Caspr2抗体相关边缘叶脑炎的免疫治疗缺乏随机对照的临床研究,目前普遍的策略是一旦在血清或脑脊液中检测到相关抗体,应在寻找潜在肿瘤的同时及时进行免疫治疗。

关键词: 钾通道, 电压门控, Isaacs综合征, Morvan综合征, 边缘叶脑炎, 克雅病

中图分类号:

R512.3

王义义, 李倩, 甄晓晗. 电压门控钾离子通道复合物抗体及其相关神经综合征[J]. 临床荟萃, 2021, 36(6): 557-561.

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https://huicui.hebmu.edu.cn/CN/Y2021/V36/I6/557

参考文献 41

[1]	Shillito P, Molenaar PC, Vincent A, et al. Acquired neuromyotonia: evidence for autoantibodies directed against K+ channels of peripheral nerves[J]. Ann Neurol, 1995, 38(5):714-722. pmid: 7486862
[2]	Liguori R, Vincent A, Clover L, et al. Morvan's syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels[J]. Brain, 2001, 124(Pt 12):2417-2426. pmid: 11701596
[3]	Buckley C, Oger J, Clover L, et al. Potassium channel antibodies in two patients with reversible limbic encephalitis[J]. Ann Neurol, 2001, 50(1):73-78. pmid: 11456313
[4]	Lai M, Huijbers MG, Lancaster E, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series[J]. Lancet Neurol, 2010, 9(8):776-785. doi: 10.1016/S1474-4422(10)70137-X URL
[5]	Irani SR, Alexander S, Waters P, et al. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan's syndrome and acquired neuromyotonia[J]. Brain, 2010, 133(9):2734-2748. doi: 10.1093/brain/awq213 URL
[6]	Schulte U, Thumfart JO, Klöcker N, et al. The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvbeta1[J]. Neuron, 2006, 49(5):697-706. pmid: 16504945
[7]	Fukata Y, Lovero KL, Iwanaga T, et al. Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy[J]. Proc Natl Acad Sci U S A, 2010, 107(8):3799-3804. doi: 10.1073/pnas.0914537107 pmid: 20133599
[8]	Savvaki M, Panagiotaropoulos T, Stamatakis A, et al. Impairment of learning and memory in TAG-1 deficient mice associated with shorter CNS internodes and disrupted juxtaparanodes[J]. Mol Cell Neurosci, 2008, 39(3):478-490. doi: 10.1016/j.mcn.2008.07.025 pmid: 18760366
[9]	Poliak S, Salomon D, Elhanany H, et al. Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1[J]. J Cell Biol, 2003, 162(6):1149-1160. doi: 10.1083/jcb.200305018 URL
[10]	Gadoth A, Pittock SJ, Dubey D, et al. Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients[J]. Ann Neurol, 2017, 82(1):79-92. doi: 10.1002/ana.24979 doi: 10.1002/ana.24979 URL pmid: 28628235
[11]	Isaacs H. A Syndrome of continuous muscle-fibre activity[J]. J Neurol Neurosurg Psychiatry, 1961, 24(4):319-325. doi: 10.1136/jnnp.24.4.319 URL
[12]	Newsom-Davis J, Mills KR. Immunological associations of acquired neuromyotonia (Isaacs' syndrome). Report of five cases and literature review[J]. Brain, 1993, 116(Pt 2):453-469. doi: 10.1093/brain/116.2.453 URL
[13]	Hart IK, Maddison P, Newsom-Davis J, et al. Phenotypic variants of autoimmune peripheral nerve hyperexcitability[J]. Brain, 2002, 125(Pt 8):1887-1895. pmid: 12135978
[14]	Gantenbein AR, Wiederkehr M, Meuli-Simmen C, et al. Focal neuromyotonia: do I love you?[J]. J Neurol, 2010, 257(10):1727-1729. doi: 10.1007/s00415-010-5612-6 pmid: 20532908
[15]	Jamora RD, Umapathi T, Tan LC. Finger flexion resembling focal dystonia in Isaacs' syndrome[J]. Parkinsonism Relat Disord, 2006, 12(1):61-63. doi: 10.1016/j.parkreldis.2005.08.003 URL
[16]	Masood W, Sitammagari KK. Morvan syndrome (Morvan Fibrillary Chorea, MFC)[M]. StatPearls Treasure Island (FL): Stat Pearls Publishing, 2020.
[17]	Irani SR, Pettingill P, Kleopa KA, et al. Morvan syndrome: Clinical and serological observations in 29 cases[J]. Ann Neurol, 2012, 72(2):241-255. doi: 10.1002/ana.v72.2 URL
[18]	郝红琳, 李胜德, 孙鹤阳, 等. 莫旺综合征睡眠障碍临床分析[J]. 中华神经科杂志, 2017, 50(8) : 590-593.
[19]	Buckley C, Oger J, Clover L, et al. Potassium channel antibodies in two patients with reversible limbic encephalitis[J]. Ann Neurol, 2001, 50(1):73-78. pmid: 11456313
[20]	Somers KJ, Lennon VA, Rundell JR, et al. Psychiatric manifestations of voltage-gated potassium-channel complex autoimmunity[J]. J Neuropsychiatry Clin Neurosci, 2011, 23(4):425-433. doi: 10.1176/jnp.23.4.jnp425 URL
[21]	Bettcher BM, Gelfand JM, Irani SR, et al. More than memory impairment in voltage-gated potassium channel complex encephalopathy[J]. Eur J Neurol, 2014, 21(10):1301-1310. doi: 10.1111/ene.12482 pmid: 24981998
[22]	Striano P. Faciobrachial dystonic attacks: seizures or movement disorder?[J]. Ann Neurol, 2011, 70(1):179-180. doi: 10.1002/ana.22470 URL
[23]	Erkmen CP, Fadul CE, Dalmau J, et al. Thymoma-associated paraneoplastic encephalitis (TAPE): diagnosis and treatment of a potentially fatal condition[J]. J Thorac Cardiovasc Surg, 2011, 141(2):e17-e20. doi: 10.1016/j.jtcvs.2010.10.022 URL
[24]	Iorio R, Assenza G, Tombini M, et al. The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy[J]. Eur J Neurol, 2015, 22(1):70-78. doi: 10.1111/ene.12529 pmid: 25112548
[25]	Marynissen T, Govers N, Vydt T. Ictal asystole: case report with review of literature[J]. Acta Cardiol, 2012, 67(4):461-464. pmid: 22998002
[26]	Lancaster E, Huijbers MG, Bar V, et al. Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia[J]. Ann Neurol, 2011, 69(2):303-311. doi: 10.1002/ana.22297 pmid: 21387375
[27]	Klein CJ, Lennon VA, Aston PA, et al. Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping[J]. JAMA Neurol, 2013, 70(2):229-234. doi: 10.1001/jamaneurol.2013.592 URL
[28]	Jammoul A, Shayya L, Mente K, et al. Clinical utility of seropositive voltage-gated potassium channel-complex antibody[J]. Neurol Clin Pract, 2016, 6(5):409-418. pmid: 27847683
[29]	Irani SR, Vincent A. Voltage-gated potassium channel-complex autoimmunity and associated clinical syndromes[J]. Handb Clin Neurol, 2016, 133:185-197.
[30]	Michael S, Waters P, Irani SR. Stop testing for autoantibodies to the VGKC-complex: only request LGI1 and CASPR2[J]. Pract Neurol, 2020 Jun 28. practneurol-2019-002494. [published online ahead of print]
[31]	Ramanathan S, Al-Diwani A, Waters P, et al. The autoantibody-mediated encephalitides: From clinical observations to molecular pathogenesis[J]. J Neurol, 2019,10.1007/s00415-019-09590-9. [published online ahead of print]
[32]	Geschwind MD, Tan KM, Lennon VA, et al. Voltage-gated potassium channel autoimmunity mimicking creutzfeldt-jakob disease[J]. Arch Neurol, 2008, 65(10):1341-1346.
[33]	Chitravas N, Jung RS, Kofskey DM, et al. Treatable neurological disorders misdiagnosed as Creutzfeldt-Jakob disease[J]. Ann Neurol, 2011, 70(3):437-444. doi: 10.1002/ana.22454 pmid: 21674591
[34]	Flanagan EP, McKeon A, Lennon VA, et al. Autoimmune dementia: Clinical course and predictors of immunotherapy response[J]. Mayo Clin Proc, 2010, 85(10):881-897. doi: 10.4065/mcp.2010.0326 pmid: 20884824
[35]	Grau-Rivera O, Sánchez-Valle R, Saiz A, et al. Determination of neuronal antibodies in suspected and definite Creutzfeldt-Jakob disease[J]. JAMA Neurol, 2014, 71(1):74-78. doi: 10.1001/jamaneurol.2013.4857 pmid: 24248099
[36]	Rossi M, Mead S, Collinge J, et al. Neuronal antibodies in patients with suspected or confirmed sporadic Creutzfeldt-Jakob disease[J]. J Neurol Neurosurg Psychiatry, 2015, 86(6):692-694. doi: 10.1136/jnnp-2014-308695 URL
[37]	Montojo MT, Petit-Pedrol M, Graus F, et al. Clinical spectrum and diagnostic value of antibodies against the potassium channel related protein complex[J]. Neurologia, 2015, 30(5):295-301. doi: 10.1016/j.nrl.2013.12.007 pmid: 24485651
[38]	van Sonderen A, Schreurs MW, de Bruijn MA, et al. The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies[J]. Neurology, 2016, 86(18):1692-1699. doi: 10.1212/WNL.0000000000002637 pmid: 27037230
[39]	Irani SR, Gelfand JM, Al-Diwani A, et al. Cell-surface central nervous system autoantibodies: Clinical relevance and emerging paradigms[J]. Ann Neurol, 2014, 76(2):168-184. doi: 10.1002/ana.v76.2 URL
[40]	Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis[J]. Ann Neurol, 2011, 69(5):892-900. doi: 10.1002/ana.v69.5 URL
[41]	Thompson J, Bi M, Murchison AG, et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures[J]. Brain, 2018, 141(2):348-356. doi: 10.1093/brain/awx323 pmid: 29272336