Abstract
Anti-neuronal antibodies that are related with autoimmune encephalitis syndromes may also be found in children with new onset seizures or chronic epilepsy. To unravel the significance of autoimmune astrocytopathy in epilepsy, we investigated serum antibody to glial fibrillary acidic protein (GFAP), another autoantigen described in autoimmune encephalitis with seizures, in 38 children with focal seizures of undetermined cause. GFAP antibody was screened with cell based assay and indirect immunohistochemistry and was found in two boys with normal brain MRI and unrevealing medical history prior to seizures. The 2-year-old boy had chronic treatment-resistant frontal lobe epilepsy. The 2.5-year-old boy had a single episode of focal seizures and remained seizure free thereafter in a follow-up period of 4 years. Nevertheless, he showed severe cognitive and language impairment. These results suggest that autoimmune astrocytopathy may be present in some epilepsy patients. Whether this immune response is a bystander effect generated by seizure-induced astrocytosis or directly involved in epileptogenesis needs to be further studied.
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References
Spatola M, Dalmau J (2017) Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Curr Opin Neurol 30:345–353. https://doi.org/10.1097/WCO.0000000000000449
Suleiman J, Wright S, Gill D, Brilot F, Waters P, Peacock K, Procopis P, Nibber A, Vincent A, Dale RC, Lang B (2013) Autoantibodies to neuronal antigens in children with new-onset seizures classified according to the revised ILAE organization of seizures and epilepsies. Epilepsia 54:2091–2100. https://doi.org/10.1111/epi.12405
Brenner T, Sills GJ, Hart Y, Howell S, Waters P, Brodie MJ, Vincent A, Lang B (2013) Prevalence of neurologic autoantibodies in cohorts of patients with new and established epilepsy. Epilepsia 54:1028–1035. https://doi.org/10.1111/epi.12127
Ekizoglu E, Tuzun E, Woodhall M, Lang B, Jacobson L, Icoz S, Bebek N, Gurses C, Gokyigit A, Waters P, Vincent A, Baykan B (2014) Investigation of neuronal autoantibodies in two different focal epilepsy syndromes. Epilepsia 55:414–422. https://doi.org/10.1111/epi.12528
Vanli-Yavuz EN, Erdag E, Tuzun E, Ekizoglu E, Baysal-Kirac L, Ulusoy C, Peach S, Gundogdu G, Sencer S, Sencer A, Kucukali CI, Bebek N, Gurses C, Gokyigit A, Baykan B (2016) Neuronal autoantibodies in mesial temporal lobe epilepsy with hippocampal sclerosis. J Neurol Neurosurg Psychiatry 87:684–692. https://doi.org/10.1136/jnnp-2016-313146
Baysal-Kirac L, Tuzun E, Erdag E, Ulusoy C, Vanli-Yavuz EN, Ekizoglu E, Peach S, Sezgin M, Bebek N, Gurses C, Gokyigit A, Vincent A, Baykan B (2016) Neuronal autoantibodies in epilepsy patients with peri-ictal autonomic findings. J Neurol 263:455–466. https://doi.org/10.1007/s00415-015-8002-2
Masdeu JC, Dalmau J, Berman KF (2016) NMDA receptor internalization by autoantibodies: a reversible mechanism underlying psychosis? Trends Neurosci 39:300–310. https://doi.org/10.1016/j.tins.2016.02.006
Hamid SHM, Whittam D, Saviour M, Alorainy A, Mutch K, Linaker S, Solomon T, Bhojak M, Woodhall M, Waters P, Appleton R, Duddy M, Jacob A (2018) Seizures and encephalitis in myelin oligodendrocyte glycoprotein IgG disease vs aquaporin 4 IgG disease. JAMA Neurol 75:65–71. https://doi.org/10.1001/jamaneurol.2017.3196
Fang B, McKeon A, Hinson SR, Kryzer TJ, Pittock SJ, Aksamit AJ, Lennon VA (2016) Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol 73:1297–1307. https://doi.org/10.1001/jamaneurol.2016.2549
Shan F, Long Y, Qiu W (2018) Autoimmune glial fibrillary acidic protein astrocytopathy: a review of the literature. Front Immunol 5(9):2802. https://doi.org/10.3389/fimmu.2018.02802
Kunchok A, Zekeridou A, McKeon A (2019) Autoimmune glial fibrillary acidic protein astrocytopathy. Curr Opin Neurol 32:452–458. https://doi.org/10.1097/WCO.0000000000000676
Long Y, Liang J, Xu H, Huang Q, Yang J, Gao C, Qiu W, Lin S, Chen X (2018) Autoimmune glial fibrillary acidic protein astrocytopathy in Chinese patients: a retrospective study. Eur J Neurol 25:477–483. https://doi.org/10.1111/ene.13531
Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde BW, Engel J, French J, Glauser TA, Mathern GW, Moshé SL, Nordli D, Plouin P, Scheffer IE (2010) Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE commission on classification and terminology, 2005–2009. Epilepsia 51:676–685. https://doi.org/10.1111/j.1528-1167.2010.02522.x
Kwan P, Schachter SC, Brodie MJ (2011) Drug-resistant epilepsy. N Engl J Med 365:919–926. https://doi.org/10.1056/NEJMra1004418
Flanagan EP, Hinson SR, Lennon VA, Fang B, Aksamit AJ, Morris PP, Basal E, Honorat JA, Alfugham NB, Linnoila JJ, Weinshenker BG, Pittock SJ, McKeon A (2017) Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: analysis of 102 patients. Ann Neurol 81:298–309. https://doi.org/10.1002/ana.24881
Finke C, Prüss H, Heine J, Reuter S, Kopp UA, Wegner F, Then Bergh F, Koch S, Jansen O, Münte T, Deuschl G, Ruprecht K, Stöcker W, Wandinger KP, Paul F, Bartsch T (2017) Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. JAMA Neurol 74:50–59. https://doi.org/10.1001/jamaneurol.2016.4226
Hébert J, Day GS, Steriade C, Wennberg RA, Tang-Wai DF (2018) Long-term cognitive outcomes in patients with autoimmune encephalitis. Can J Neurol Sci 45:540–544. https://doi.org/10.1017/cjn.2018.33
Rubio-Agustí I, Dalmau J, Sevilla T, Burgal M, Beltrán E, Bataller L (2011) Isolated hemidystonia associated with NMDA receptor antibodies. Mov Disord 26:351–352. https://doi.org/10.1002/mds.23315
Erer Özbek S, Yapıcı Z, Tüzün E, Giriş M, Duran S, Taşkapılıoğlu Ö, Okan M (2015) A case of hyperkinetic movement disorder associated with LGI1 antibodies. Turk J Pediatr 57:514–517
Dalmau J, Armangué T, Planagumà J, Radosevic M, Mannara F, Leypoldt F, Geis C, Lancaster E, Titulaer MJ, Rosenfeld MR, Graus F (2019) An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models. Lancet Neurol. https://doi.org/10.1016/S1474-4422(19)30244-3
Freund B, Ritzl EK (2019) A review of EEG in anti-NMDA receptor encephalitis. J Neuroimmunol 332:64–68. https://doi.org/10.1016/j.jneuroim.2019.03.010
Li D, Li P, He Z, Cen D, Meng Z, Liang L, Luo X (2012) Human intravenous immunoglobulins suppress seizure activities and inhibit the activation of GFAP-positive astrocytes in the hippocampus of picrotoxin-kindled rats. Int J Neurosci 122:200–208. https://doi.org/10.3109/00207454.2011.639470
Simani L, Elmi M, Asadollahi M (2018) Serum GFAP level: a novel adjunctive diagnostic test in differentiate epileptic seizures from psychogenic attacks. Seizure 61:41–44. https://doi.org/10.1016/j.seizure.2018.07.010
Yang X, Xu H, Ding M, Huang Q, Chen B, Yang H, Liu T, Long Y, Gao C (2018) Overlapping autoimmune syndromes in patients with glial fibrillary acidic protein antibodies. Front Neurol 25(9):251. https://doi.org/10.3389/fneur.2018.00251
Funding
This study was funded by the Istanbul University Scientific Research Fund (Grant No. 50370, 2015) and Greek Operational Programme Competitiveness Entrepreneurship and Innovation 2014 2020 program (EPANEK) (Grant No. Τ1ΕΔΚ-05024).
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Savaş, M., Tzartos, J., Küçükali, C.İ. et al. Glial fibrillary acidic protein (GFAP)-antibody in children with focal seizures of undetermined cause. Acta Neurol Belg 121, 1275–1280 (2021). https://doi.org/10.1007/s13760-020-01361-y
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DOI: https://doi.org/10.1007/s13760-020-01361-y