自身免疫起源的迟发性癫痫流行率和临床结局：一项前瞻性观察性人群队列研究_Journal of Epilepsy

Authors：

 Felix vonPodewils , MarieSuesse , JuliaGeithner , 张颖颖　译 , 童馨　慕洁　审

Corresponding author：

Felix vonPodewils, Email: felix.podewils@uni-greifswald.de

Keywords：

自身免疫性病因; 迟发型癫痫; 神经元抗体

DOI：

10.7507/2096-0247.20180043

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

众所周知，随着年龄增长新发癫痫的发病率增加。通常，这些患者的病因难以明确。研究调查了有非诱导性迟发性癫痫发作且不合并肿瘤（可能患有副肿瘤性脑炎）患者的潜在自身免疫反应情况。在 4.75 年内前瞻性连续纳入了 66 例患者（至少有一次癫痫或癫痫发作，病程≤6 个月，36 例女性，年龄≥55 岁）。检测所有患者的血清、脑脊液抗体和神经细胞表面、细胞内抗原。45 例患者（68%）进行了核磁共振（MRI）检查。对于抗体阳性的患者随访时间至少 6 个月。2 例患者血清、脑脊液中抗接触蛋白相关性蛋白样-2（Contactin associated protein-like 2, CASPR2）抗体滴度高，符合明确边缘性脑炎的诊断标准。另外 2 例患者 MRI 显示双侧脑颞区炎性异常，尽管血清、脑脊液抗体阴性，也符合明确边缘性脑炎的诊断标准。这 4 例患者年龄 55～70 岁之间，均接受了抗免疫治疗和（或）抗癫痫治疗之后变成癫痫再无发作。该研究发现提示自身免疫应该被认为是迟发型癫痫患者的一个重要病因。对于这些患者，神经元抗体检测和大脑 MRI 可能是有价值的检查手段。

Citation： Felix vonPodewils, MarieSuesse, JuliaGeithner, 张颖颖　译, 童馨　慕洁　审. 自身免疫起源的迟发性癫痫流行率和临床结局：一项前瞻性观察性人群队列研究. Journal of Epilepsy, 2018, 4(3): 242-248. doi: 10.7507/2096-0247.20180043 Copy

1.	Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in rochester, Minnesota: 1935-1984. Epilepsia, 1993, 34(3): 453-468.
2.	Olafsson E, Ludvigsson P, Gudmundsson G, et al. Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study. Lancet Neurol, 2005, 4(10): 627-634.
3.	Spatola M, Dalmau J. Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Curr Opin Neurol, 2017, 30(3): 345-353.
4.	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. Brain, 2010, 133(9): 2734-2748.
5.	Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol, 2016, 15(4): 391-404.
6.	Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain, 2000, 123(7): 1481-1494.
7.	Bien CG, Schulze-Bonhage A, Deckert M, et al. Limbic encephalitis not associated with neoplasm as a cause of temporal lobe epilepsy. Neurology, 2000, 55(12): 1823-1828.
8.	Vincent A, Buckley C, Schott JM, et al. Potassium channel antibodyassociatedencephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain, 2004, 127(Pt 3): 701-712.
9.	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. Lancet Neurol, 2010, 9(8): 776-785.
10.	Lai M, Hughes EG, Peng X, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol, 2009, 65(4): 424-434.
11.	Carvajal-Gonzalez A, Leite MI, Waters P, et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain, 2014, 137(Pt 8): 2178-2192.
12.	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. Ann Neurol, 2013, 73(1): 120-128.
13.	Lancaster E, Martinez-Hernandez E, Titulaer MJ, et al. Antibodies to metabotropic glutamate receptor 5 in the ophelia syndrome. Neurology, 2011, 77(18): 1698-1701.
14.	Lancaster E, Lai M, Peng X, et al. Antibodies to the GABA(b) receptor in l imbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol, 2010, 9(1): 67-76.
15.	Malter MP, Helmstaedter C, Urbach H, et al. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol, 2010, 67(4): 470-478.
16.	Stefan H, May TW, Pfafflin M, et al. Epilepsy in the elderly: comparingclinical characteristics with younger patients. Acta Neurol Scand, 2014, 129(5): 283-293.
17.	Bien CG, Mirzadjanova Z, Baumgartner C, et al. Anti-contactin-associated protein-2 encephalitis: relevance of antibody titres, presentation and outcome. Eur J Neurol, 2017, 24(1): 175-186.
18.	van Sonderen A, Schreurs MW, de Bruijn MA, et al. The relevance of VGKC positivity in the absence of LGI1 and caspr2 antibodies. Neurology, 2016, 86(18): 1692-1699.
19.	Lang B, Makuch M, Moloney T, et al. Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies. J Neurol Neurosurg Psychiatry, 2017, 88(4): 353-361.
20.	Bataller L, Kleopa KA, Wu GF, et al. Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes. J Neurol Neurosurg Psychiatry, 2007, 78(4): 381-385.
21.	van Sonderen A, Ari~no H, Petit-Pedrol M, et al. The clinical spectrum of caspr2 antibody-associated disease. Neurology, 2016, 87(5): 521-528.
22.	van Sonderen A, Schreurs MWJ, Wirtz PW, et al. From VGKC to LGI1 and CASPR2 encephalitis: the evolution of a disease entity over time. Autoimmun Rev, 2016, 15(10): 970-974.
23.	Joubert B, Saint-Martin M, Noraz N, et al. Characterization of a subtype of autoimmune encephalitis with anti-contactinassociated protein-like2 antibodies in the cerebrospinal fluid, prominent limbic symptoms, and seizures. JAMA Neurol, 2016, 73(9): 1115-1124.
24.	da Rocha AJ, Nunes RH, Maia ACM, et al. Recognizing autoimmunemediated encephalitis in the differential diagnosis of limbic disorders. AJNR Am J Neuroradiol, 2015, 36(12): 2196-2205.
25.	Urbach H, Soeder BM, Jeub M, et al. Serial MRI of limbic encephalitis. Neuroradiology, 2006, 48(6): 380-386.
26.	Leypoldt F, Armangue T, Dalmau J. Autoimmune encephalopathies. Ann N Y Acad Sci, 2015, 1338: 94-114.
27.	Huda S, Wong SH, Pettingill P, et al. An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre. J Neurol, 2015, 262(2): 418-424.

1. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in rochester, Minnesota: 1935-1984. Epilepsia, 1993, 34(3): 453-468.
2. Olafsson E, Ludvigsson P, Gudmundsson G, et al. Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study. Lancet Neurol, 2005, 4(10): 627-634.
3. Spatola M, Dalmau J. Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Curr Opin Neurol, 2017, 30(3): 345-353.
4. 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. Brain, 2010, 133(9): 2734-2748.
5. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol, 2016, 15(4): 391-404.
6. Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain, 2000, 123(7): 1481-1494.
7. Bien CG, Schulze-Bonhage A, Deckert M, et al. Limbic encephalitis not associated with neoplasm as a cause of temporal lobe epilepsy. Neurology, 2000, 55(12): 1823-1828.
8. Vincent A, Buckley C, Schott JM, et al. Potassium channel antibodyassociatedencephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain, 2004, 127(Pt 3): 701-712.
9. 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. Lancet Neurol, 2010, 9(8): 776-785.
10. Lai M, Hughes EG, Peng X, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol, 2009, 65(4): 424-434.
11. Carvajal-Gonzalez A, Leite MI, Waters P, et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain, 2014, 137(Pt 8): 2178-2192.
12. 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. Ann Neurol, 2013, 73(1): 120-128.
13. Lancaster E, Martinez-Hernandez E, Titulaer MJ, et al. Antibodies to metabotropic glutamate receptor 5 in the ophelia syndrome. Neurology, 2011, 77(18): 1698-1701.
14. Lancaster E, Lai M, Peng X, et al. Antibodies to the GABA(b) receptor in l imbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol, 2010, 9(1): 67-76.
15. Malter MP, Helmstaedter C, Urbach H, et al. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol, 2010, 67(4): 470-478.
16. Stefan H, May TW, Pfafflin M, et al. Epilepsy in the elderly: comparingclinical characteristics with younger patients. Acta Neurol Scand, 2014, 129(5): 283-293.
17. Bien CG, Mirzadjanova Z, Baumgartner C, et al. Anti-contactin-associated protein-2 encephalitis: relevance of antibody titres, presentation and outcome. Eur J Neurol, 2017, 24(1): 175-186.
18. van Sonderen A, Schreurs MW, de Bruijn MA, et al. The relevance of VGKC positivity in the absence of LGI1 and caspr2 antibodies. Neurology, 2016, 86(18): 1692-1699.
19. Lang B, Makuch M, Moloney T, et al. Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies. J Neurol Neurosurg Psychiatry, 2017, 88(4): 353-361.
20. Bataller L, Kleopa KA, Wu GF, et al. Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes. J Neurol Neurosurg Psychiatry, 2007, 78(4): 381-385.
21. van Sonderen A, Ari~no H, Petit-Pedrol M, et al. The clinical spectrum of caspr2 antibody-associated disease. Neurology, 2016, 87(5): 521-528.
22. van Sonderen A, Schreurs MWJ, Wirtz PW, et al. From VGKC to LGI1 and CASPR2 encephalitis: the evolution of a disease entity over time. Autoimmun Rev, 2016, 15(10): 970-974.
23. Joubert B, Saint-Martin M, Noraz N, et al. Characterization of a subtype of autoimmune encephalitis with anti-contactinassociated protein-like2 antibodies in the cerebrospinal fluid, prominent limbic symptoms, and seizures. JAMA Neurol, 2016, 73(9): 1115-1124.
24. da Rocha AJ, Nunes RH, Maia ACM, et al. Recognizing autoimmunemediated encephalitis in the differential diagnosis of limbic disorders. AJNR Am J Neuroradiol, 2015, 36(12): 2196-2205.
25. Urbach H, Soeder BM, Jeub M, et al. Serial MRI of limbic encephalitis. Neuroradiology, 2006, 48(6): 380-386.
26. Leypoldt F, Armangue T, Dalmau J. Autoimmune encephalopathies. Ann N Y Acad Sci, 2015, 1338: 94-114.
27. Huda S, Wong SH, Pettingill P, et al. An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre. J Neurol, 2015, 262(2): 418-424.

Previous Article
DNA 甲基化在癫痫中的研究进展
Next Article
使用表皮肌电监测来检测全面强直-阵挛发作

Journal of Epilepsy

自身免疫起源的迟发性癫痫流行率和临床结局：一项前瞻性观察性人群队列研究

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content