抗谷氨酸脱羧酶 65 抗体相关癫痫发作的研究进展_Journal of Epilepsy

Authors：

樊雪梅 , 李鑫鑫 , 黄贤会 ,  刘松岩

吉林大学中日联谊医院神经内科（长春 130033）;

Corresponding author：

刘松岩, Email: Liu_sy@jlu.edu.cn

Keywords：

DOI：

10.7507/2096-0247.20210038

Video：

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癫痫发作是一系列免疫介导的神经系统疾病谱的一部分，随着神经免疫学的发展和抗神经元抗体检测技术的提高，自身免疫性脑炎（Autoimmune encephalitis，AE）相关抗体介导的癫痫发作比以往认为的更加普遍，抗谷氨酸脱羧酶（Glutamic acid decarboxylase，GAD）65 抗体也是成人不明原因的药物难治性癫痫患者中常检测到的抗体之一。目前，国内对于抗 GAD65 抗体相关癫痫发作研究较少，临床医生对其缺乏进一步的认识，使得临床上可能存在漏诊，患者的病情未能得到及时的治疗。文章结合国内外最新研究，对抗 GAD65 抗体相关癫痫发作的流行病学、病理生理学、临床表现、治疗及预后方面做一综述，为临床诊治提供参考。

Citation： 樊雪梅, 李鑫鑫, 黄贤会, 刘松岩. 抗谷氨酸脱羧酶 65 抗体相关癫痫发作的研究进展. Journal of Epilepsy, 2021, 7(3): 246-251. doi: 10.7507/2096-0247.20210038 Copy

1.	Steriade C, Britton J, Dale R, et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune associated epilepsy: Conceptual definitions. Epilepsia, 2020, 61(7): 1341-1351.
2.	Malter MP, Helmstaedter C, Urbach H, et al. Antibodies to glutamic acid decarboxylase deﬁne a form of limbic encephalitis. Ann Neurol, 2010, 67: 470-478.
3.	Dubey D, Alqallaf A, Hays R, et al. Neurologicalauto an-tibody prevalence in epilepsy of unknown etiology. JAMANeurol, 2017, 74: 397-402.
4.	Lilleker JB, Biswas V, Mohanraj R. Glutamic acid decarboxylase (GAD) antibodies in epilepsy: diagnostic yield and therapeutic implications. Seizure, 2014, 23: 598-602.
5.	McKnight K, Jiang Y, Hart Y, et al. Serum antibodies in epilepsy and seizure-associated disorders. Neurology, 2005, 65(11): 1730-1736.
6.	Reetz A, Solimena M, Matteoli M, et al. GABA and pancreatic beta-cells: colocalization of glutamic acid decarboxylase (GAD) and GABA with synaptic-like microvesicles suggests their role in GABA storage and secretion. EMBO J, 1991, 10: 1275-1284.
7.	Kass I, Hoke DE, Costa MG, et al. Cofactor-dependent conformational heterogeneity of GAD65 and its role in autoimmunity and neurotransmitter homeostasis. Proc Natl Acad Sci USA, 2014, 111(25): E2524-2529.
8.	Fenalti G, Hampe CS, Arafat Y; et al. COOH-terminal clustering of autoantibody and T-cell determinants on the structure of GAD65 provide insights into the molecular basis of autoreactivity. Diabetes, 2008, 57(5): 1293-1301.
9.	Fenalti G, Buckle AM. Structural biology of the GAD autoantigen. Autoimmun Rev, 2010, 9(3): 148-152.
10.	Ali F, Rowley M, JayakrishnanB, et al. Stiff-person syndrome (SPS) and anti-GAD-related CNS degenerations: protean additions to the autoimmune central neuropathies. J Autoimmun, 2011, 37: 79-87.
11.	Richter W, Shi Y, Baekkeskov S. Autoreactive epitopes defined by diabetes-associated human monoclonal antibodies are localized in the middle and C-terminal domains of the smaller form of glutamate decarboxylase. Proc Natl Acad Sci USA, 1993, 90: 2832-2836.
12.	Petit-Pedrol M, Sabater L, Saiz A, et al. Antibodies to inhibitory synaptic proteins in neurological syndromes associated with glutamic acid decarboxylase autoimmunity. PLoS One, 2015, 10: e0121364.
13.	Xinxin Li, Qi Guo, Songyan Liu, et al. Immune-mediated epilepsy with GAD65 antibodies. J Neuroimmunol, 2020, 341: 577189.
14.	Ahmad Daif, RimasV Lukas, Naoum P, et al. Antiglutamic acid decarboxylase 65(GAD65)antibody-associated epilepsy. Epilepsy Behav, 2018, 80: 331-336.
15.	Bien CG, Vincent A, Barnett MH, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain, 2012, 135: 1622-1638.
16.	Waterhouse NJ, Sutton VR, Sedelies KA, et al. Cytotoxic T lymphocyte-induced killing in the absence of granzymes A and B is unique and distinct from both apoptosis and perforin-dependent lysis. J Cell Biol, 2006, 173: 133-144.
17.	Meuth SG, Herrmann AM, Simon OJ, et al. Cytotoxic CD8+ T cell-neuron interactions: perforin-dependent electrical silencing precedes but is not causally linked to neuronal cell death. J Neurosci, 2009, 29: 15397-15409.
18.	Widman G, Golombeck K, Hautzel H, et al. Treating a GAD65 antibody-associated limbic encephalitis with Basiliximab: a case study. Front Neurol, 2015, 6: 167.
19.	Vogrig A, Joubert B, André-ObadiaN, et al. Seizure specificities in patients with antibody-mediated autoimmune encephalitis. Epilepsia, 2019, 60(8): 1508-1525.
20.	Errichiello L, Perruolo G, Pascarella A, et al. Autoantibodies to glutamic acid decarboxylase (GAD) in focal and generalized epilepsy: a study on 233 patients. J Neuroimmunol, 2009, 211: 120-123.
21.	Bien CG, Urbach H, Schramm J, et al. Limbic encephalitis as a precipitating event in adult-onset temporal lobe epilepsy. Neurology, 2007, 69: 1236-1244.
22.	刘丹丹, 邵晓秋译; 吴逊, 关鸿志审. 继发于自身免疫性脑炎的急性症状性发作和自身免疫相关癫痫: 概念性定义. 癫痫杂志, 2020, 9(6): 443-450.
23.	徐雯, 苗晶, 白晶, 等. 抗谷氨酸脱羧酶(GAD65)抗体相关脑炎 1 例报告并文献复习. 中风与神经病学杂志, 2019, 2(36): 165-166.
24.	余年, 王凌玲, 苗爱亮, 等. 抗谷氨酸脱羧酶抗体阳性自身免疫性脑炎三例临床特征分析. 中国神经免疫学和神经病学杂志, 2020, 3(27): 122-128.
25.	王亮. 22 例自身免疫性癫痫的临床特征. 河北医科大学硕士学位论文. 2020.
26.	BastienJoubert, AudeBelbezier, Julie Haesebaert, et al. Long-term outcomes in temporal lobe epilepsy with glutamate decarboxylase antibodies. Journal of Neurology, 2020, 267(7): 2083-2089.
27.	李承玉, 刘丹丹, 邵晓秋, 等. 谷氨酸脱羧酶 65 抗体相关自身免疫性癫痫的临床、影像学和脑电图特征. 第八届CEEA国际癫痫论坛, 2019.
28.	王小鹏, 韩曙光, 唐海, 等. 抗 GAD65 抗体脑炎的临床特点. 国际感染病学(电子版), 2019, 8(04): 128-129.
29.	Falip M, Rodriguez-Bel L, CastañerS, et al. Musicogenic reflex seizures in epilepsy with glutamic acid decarbocylase antibodies. ActaNeurolScand, 2018, 137(2): 272-276.
30.	Kammeyer R, Piquet AL. Multiple co-existing antibodies in autoimmune en- cephalitis: a case and review of the literature. J Neuroimmuno, 2019, 337: 577084.
31.	Gagnon MM, Savard M, Mourabit Amari K. Refractory status epilepticus and autoimmune encephalitis with GABAAR and GAD65 antibodies: a case report. Seizure, 2016, 37: 25-27.
32.	Höftberger R, Titulaer MJ, Sabater L, et al. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology, 2013, 81(17): 1500-1506.
33.	樊雪梅, 刘松岩, 黄丽敏, 等. 抗富含亮氨酸胶质瘤失活蛋白 1、谷氨酸脱羧酶 65 抗体双重阳性自身免疫性脑炎并白癜风一例. 中华神经科杂志, 2020, 53(10): 810-813.
34.	Ariño H, Höftberger R, Gresa-Arribas N, et al. Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol, 2015, 72(8): 874-881.
35.	Zekeridou A, Majed M, HeliopoulosI, et al. Paraneoplastic autoimmunity and small-cell lung cancer: Neurological and serological accompaniments. Thorac Cancer, 2019, 10(4): 1001-1004.
36.	McKeon A, Tracy JA. GAD65 neurological autoimmunity. Muscle Nerve, 2017, 56(1): 15-27.
37.	Pittock S J, Kryzer T J, Lennon V A, et al. Paraneoplastic antibodies coexist and pre- dict cancer, not neurological syndrome. Ann Neurol, 2004, 56(5): 715-719.
38.	Gagnon MM, Savard M. Limbic encephalitis associated with GAD65 antibodies: brief review of the relevant literature. Can J Neurol Sci, 2016, 43(4): 486-493.
39.	Ren HT, Liu HQ, Qu T, et al. Autoimmune encephalitis associated with vitiligo? J Neuroimmunol, 2017, 310: 14-16.
40.	Liimatainen S, et al. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia, 2010, 51(5): 760-767.
41.	Quek AM, Britton JW, McKeon A, et al. Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol, 2012, 69(5): 582-593.
42.	Zhao J, Wang C, Xu X, et al. Coexistence of autoimmune encephalitis and other systemic autoimmune diseases. Front Neurol, 2019, 10: 1142.
43.	Saiz A, Blanco Y, Sabater L, et al. Spectrumof neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain, 2008, 131: 2553-2563.
44.	Dalakas MC, Li M, FujiiM, et al. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology, 2001, 57(5): 780-784.
45.	FauserS, UttnerI, Ariño H, et al. Long latency between GAD-antibody detection and development of limbic encephalitis - a case report. BMC Neurol, 2015, 15(1): 177.
46.	KwanP, Sills GJ, Kelly K, et al. Glutamic acid decarboxylase autoantibodies in controlled and uncontrolled epilepsy: a pilot study. Epilepsy Res, 2000, 42: 191-195.
47.	Nociti V, Frisullo G, Tartaglione T, et al. Refractory generalized seizures and cerebellar ataxia associated with anti-GAD antibodies responsive to immunosuppressive treatment. Eur J Neurol, 2010, 17: e5.
48.	Budhram A, Leung A, Nicolle MW, et al. Diagnosing autoimmune limbic encephalitis. CMAJ, 2019, 191(19): E529-E534.
49.	Husari KS, Dubey D. Autoimmune epilepsy. Neurotherapeutics, 2019, 16(3): 685-702.
50.	Farooqi MS, Lai Y, Lancaster E, et al. Therapeutic plasma exchange and immunosuppressive therapy in a patient with anti-GAD antibody-related epilepsy: quantification of the antibody response. J Clin Apher, 2015, 30(1): 8-14.
51.	Dubey D, Konikkara J, Modur PN, et al. Effectiveness of multimodality treatment for autoimmune limbic epilepsy. Epileptic Disord, 2014, 16(4): 494-499.
52.	Blanc F, Ruppert E, Kleitz C, et al. Acute limbic encephalitis and glutamic acid decarboxylase antibodies: a reality? J Neurol Sci, 2009, 287: 69-71.
53.	Vulliemoz S, Vanini G, Truffert A, et al. Epilepsy and cerebellar ataxia associated with anti-glutamic acid decarboxylase antibodies. J Neurol Neurosurg Psychiatry, 2007, 78: 187-189.
54.	Iorio R, Assenza G, Tombini M, et al. The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy. European Journal of Neurology, 2015, 22(1): 70-78.
55.	Khawaja AM, Vines BL, Miller DW, et al. Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes. Epileptic Disord, 2016, 18: 34-43.
56.	Crom WR, Glynn-Barnhart AM, Rodman JH, et al. Pharmacokinetics of anticancer drugs in children. Clin Pharmacokinet, 1987, 12: 168-213.
57.	Holzer FJ, Rossetti AO, Heritier-Barras AC, et al. Antibody-mediated status epilepticus: a retrospective multicenter survey. Eur Neurol, 2012, 68: 310-317.
58.	Dubey D, Farzal Z, Hays R, et al. Evaluation of positive and negative predictors of seizure outcomes among patients with immune-mediated epilepsy: a meta-analysis. Therapeutic Advances in Neurological Disorders, 2016, 9(5): 369-377.
59.	Blum S, Dionisio S. Refractory epilepsy secondary to anti-GAD encephalitis treated with DBS post SEEG evaluation: a novel case report based on stimulation findings. Epileptic Disord, 2018, 20(5): 451-456.
60.	Feyissa AM, Mirro EA, Wabulya A, et al. Brain-responsive neurostimulation treatment in patients with GAD65 antibody-associated autoimmune mesial temporal lobe epilepsy. Epilepsia Open, 2020, 5(2): 307-313.

1. Steriade C, Britton J, Dale R, et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune associated epilepsy: Conceptual definitions. Epilepsia, 2020, 61(7): 1341-1351.
2. Malter MP, Helmstaedter C, Urbach H, et al. Antibodies to glutamic acid decarboxylase deﬁne a form of limbic encephalitis. Ann Neurol, 2010, 67: 470-478.
3. Dubey D, Alqallaf A, Hays R, et al. Neurologicalauto an-tibody prevalence in epilepsy of unknown etiology. JAMANeurol, 2017, 74: 397-402.
4. Lilleker JB, Biswas V, Mohanraj R. Glutamic acid decarboxylase (GAD) antibodies in epilepsy: diagnostic yield and therapeutic implications. Seizure, 2014, 23: 598-602.
5. McKnight K, Jiang Y, Hart Y, et al. Serum antibodies in epilepsy and seizure-associated disorders. Neurology, 2005, 65(11): 1730-1736.
6. Reetz A, Solimena M, Matteoli M, et al. GABA and pancreatic beta-cells: colocalization of glutamic acid decarboxylase (GAD) and GABA with synaptic-like microvesicles suggests their role in GABA storage and secretion. EMBO J, 1991, 10: 1275-1284.
7. Kass I, Hoke DE, Costa MG, et al. Cofactor-dependent conformational heterogeneity of GAD65 and its role in autoimmunity and neurotransmitter homeostasis. Proc Natl Acad Sci USA, 2014, 111(25): E2524-2529.
8. Fenalti G, Hampe CS, Arafat Y; et al. COOH-terminal clustering of autoantibody and T-cell determinants on the structure of GAD65 provide insights into the molecular basis of autoreactivity. Diabetes, 2008, 57(5): 1293-1301.
9. Fenalti G, Buckle AM. Structural biology of the GAD autoantigen. Autoimmun Rev, 2010, 9(3): 148-152.
10. Ali F, Rowley M, JayakrishnanB, et al. Stiff-person syndrome (SPS) and anti-GAD-related CNS degenerations: protean additions to the autoimmune central neuropathies. J Autoimmun, 2011, 37: 79-87.
11. Richter W, Shi Y, Baekkeskov S. Autoreactive epitopes defined by diabetes-associated human monoclonal antibodies are localized in the middle and C-terminal domains of the smaller form of glutamate decarboxylase. Proc Natl Acad Sci USA, 1993, 90: 2832-2836.
12. Petit-Pedrol M, Sabater L, Saiz A, et al. Antibodies to inhibitory synaptic proteins in neurological syndromes associated with glutamic acid decarboxylase autoimmunity. PLoS One, 2015, 10: e0121364.
13. Xinxin Li, Qi Guo, Songyan Liu, et al. Immune-mediated epilepsy with GAD65 antibodies. J Neuroimmunol, 2020, 341: 577189.
14. Ahmad Daif, RimasV Lukas, Naoum P, et al. Antiglutamic acid decarboxylase 65(GAD65)antibody-associated epilepsy. Epilepsy Behav, 2018, 80: 331-336.
15. Bien CG, Vincent A, Barnett MH, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain, 2012, 135: 1622-1638.
16. Waterhouse NJ, Sutton VR, Sedelies KA, et al. Cytotoxic T lymphocyte-induced killing in the absence of granzymes A and B is unique and distinct from both apoptosis and perforin-dependent lysis. J Cell Biol, 2006, 173: 133-144.
17. Meuth SG, Herrmann AM, Simon OJ, et al. Cytotoxic CD8+ T cell-neuron interactions: perforin-dependent electrical silencing precedes but is not causally linked to neuronal cell death. J Neurosci, 2009, 29: 15397-15409.
18. Widman G, Golombeck K, Hautzel H, et al. Treating a GAD65 antibody-associated limbic encephalitis with Basiliximab: a case study. Front Neurol, 2015, 6: 167.
19. Vogrig A, Joubert B, André-ObadiaN, et al. Seizure specificities in patients with antibody-mediated autoimmune encephalitis. Epilepsia, 2019, 60(8): 1508-1525.
20. Errichiello L, Perruolo G, Pascarella A, et al. Autoantibodies to glutamic acid decarboxylase (GAD) in focal and generalized epilepsy: a study on 233 patients. J Neuroimmunol, 2009, 211: 120-123.
21. Bien CG, Urbach H, Schramm J, et al. Limbic encephalitis as a precipitating event in adult-onset temporal lobe epilepsy. Neurology, 2007, 69: 1236-1244.
22. 刘丹丹, 邵晓秋译; 吴逊, 关鸿志审. 继发于自身免疫性脑炎的急性症状性发作和自身免疫相关癫痫: 概念性定义. 癫痫杂志, 2020, 9(6): 443-450.
23. 徐雯, 苗晶, 白晶, 等. 抗谷氨酸脱羧酶(GAD65)抗体相关脑炎 1 例报告并文献复习. 中风与神经病学杂志, 2019, 2(36): 165-166.
24. 余年, 王凌玲, 苗爱亮, 等. 抗谷氨酸脱羧酶抗体阳性自身免疫性脑炎三例临床特征分析. 中国神经免疫学和神经病学杂志, 2020, 3(27): 122-128.
25. 王亮. 22 例自身免疫性癫痫的临床特征. 河北医科大学硕士学位论文. 2020.
26. BastienJoubert, AudeBelbezier, Julie Haesebaert, et al. Long-term outcomes in temporal lobe epilepsy with glutamate decarboxylase antibodies. Journal of Neurology, 2020, 267(7): 2083-2089.
27. 李承玉, 刘丹丹, 邵晓秋, 等. 谷氨酸脱羧酶 65 抗体相关自身免疫性癫痫的临床、影像学和脑电图特征. 第八届CEEA国际癫痫论坛, 2019.
28. 王小鹏, 韩曙光, 唐海, 等. 抗 GAD65 抗体脑炎的临床特点. 国际感染病学(电子版), 2019, 8(04): 128-129.
29. Falip M, Rodriguez-Bel L, CastañerS, et al. Musicogenic reflex seizures in epilepsy with glutamic acid decarbocylase antibodies. ActaNeurolScand, 2018, 137(2): 272-276.
30. Kammeyer R, Piquet AL. Multiple co-existing antibodies in autoimmune en- cephalitis: a case and review of the literature. J Neuroimmuno, 2019, 337: 577084.
31. Gagnon MM, Savard M, Mourabit Amari K. Refractory status epilepticus and autoimmune encephalitis with GABAAR and GAD65 antibodies: a case report. Seizure, 2016, 37: 25-27.
32. Höftberger R, Titulaer MJ, Sabater L, et al. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology, 2013, 81(17): 1500-1506.
33. 樊雪梅, 刘松岩, 黄丽敏, 等. 抗富含亮氨酸胶质瘤失活蛋白 1、谷氨酸脱羧酶 65 抗体双重阳性自身免疫性脑炎并白癜风一例. 中华神经科杂志, 2020, 53(10): 810-813.
34. Ariño H, Höftberger R, Gresa-Arribas N, et al. Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol, 2015, 72(8): 874-881.
35. Zekeridou A, Majed M, HeliopoulosI, et al. Paraneoplastic autoimmunity and small-cell lung cancer: Neurological and serological accompaniments. Thorac Cancer, 2019, 10(4): 1001-1004.
36. McKeon A, Tracy JA. GAD65 neurological autoimmunity. Muscle Nerve, 2017, 56(1): 15-27.
37. Pittock S J, Kryzer T J, Lennon V A, et al. Paraneoplastic antibodies coexist and pre- dict cancer, not neurological syndrome. Ann Neurol, 2004, 56(5): 715-719.
38. Gagnon MM, Savard M. Limbic encephalitis associated with GAD65 antibodies: brief review of the relevant literature. Can J Neurol Sci, 2016, 43(4): 486-493.
39. Ren HT, Liu HQ, Qu T, et al. Autoimmune encephalitis associated with vitiligo? J Neuroimmunol, 2017, 310: 14-16.
40. Liimatainen S, et al. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia, 2010, 51(5): 760-767.
41. Quek AM, Britton JW, McKeon A, et al. Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol, 2012, 69(5): 582-593.
42. Zhao J, Wang C, Xu X, et al. Coexistence of autoimmune encephalitis and other systemic autoimmune diseases. Front Neurol, 2019, 10: 1142.
43. Saiz A, Blanco Y, Sabater L, et al. Spectrumof neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain, 2008, 131: 2553-2563.
44. Dalakas MC, Li M, FujiiM, et al. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology, 2001, 57(5): 780-784.
45. FauserS, UttnerI, Ariño H, et al. Long latency between GAD-antibody detection and development of limbic encephalitis - a case report. BMC Neurol, 2015, 15(1): 177.
46. KwanP, Sills GJ, Kelly K, et al. Glutamic acid decarboxylase autoantibodies in controlled and uncontrolled epilepsy: a pilot study. Epilepsy Res, 2000, 42: 191-195.
47. Nociti V, Frisullo G, Tartaglione T, et al. Refractory generalized seizures and cerebellar ataxia associated with anti-GAD antibodies responsive to immunosuppressive treatment. Eur J Neurol, 2010, 17: e5.
48. Budhram A, Leung A, Nicolle MW, et al. Diagnosing autoimmune limbic encephalitis. CMAJ, 2019, 191(19): E529-E534.
49. Husari KS, Dubey D. Autoimmune epilepsy. Neurotherapeutics, 2019, 16(3): 685-702.
50. Farooqi MS, Lai Y, Lancaster E, et al. Therapeutic plasma exchange and immunosuppressive therapy in a patient with anti-GAD antibody-related epilepsy: quantification of the antibody response. J Clin Apher, 2015, 30(1): 8-14.
51. Dubey D, Konikkara J, Modur PN, et al. Effectiveness of multimodality treatment for autoimmune limbic epilepsy. Epileptic Disord, 2014, 16(4): 494-499.
52. Blanc F, Ruppert E, Kleitz C, et al. Acute limbic encephalitis and glutamic acid decarboxylase antibodies: a reality? J Neurol Sci, 2009, 287: 69-71.
53. Vulliemoz S, Vanini G, Truffert A, et al. Epilepsy and cerebellar ataxia associated with anti-glutamic acid decarboxylase antibodies. J Neurol Neurosurg Psychiatry, 2007, 78: 187-189.
54. Iorio R, Assenza G, Tombini M, et al. The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy. European Journal of Neurology, 2015, 22(1): 70-78.
55. Khawaja AM, Vines BL, Miller DW, et al. Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes. Epileptic Disord, 2016, 18: 34-43.
56. Crom WR, Glynn-Barnhart AM, Rodman JH, et al. Pharmacokinetics of anticancer drugs in children. Clin Pharmacokinet, 1987, 12: 168-213.
57. Holzer FJ, Rossetti AO, Heritier-Barras AC, et al. Antibody-mediated status epilepticus: a retrospective multicenter survey. Eur Neurol, 2012, 68: 310-317.
58. Dubey D, Farzal Z, Hays R, et al. Evaluation of positive and negative predictors of seizure outcomes among patients with immune-mediated epilepsy: a meta-analysis. Therapeutic Advances in Neurological Disorders, 2016, 9(5): 369-377.
59. Blum S, Dionisio S. Refractory epilepsy secondary to anti-GAD encephalitis treated with DBS post SEEG evaluation: a novel case report based on stimulation findings. Epileptic Disord, 2018, 20(5): 451-456.
60. Feyissa AM, Mirro EA, Wabulya A, et al. Brain-responsive neurostimulation treatment in patients with GAD65 antibody-associated autoimmune mesial temporal lobe epilepsy. Epilepsia Open, 2020, 5(2): 307-313.

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抗谷氨酸脱羧酶 65 抗体相关癫痫发作的研究进展

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