Neuronal autoantibodies in focal epilepsy with or without mesial temporal sclerosis

  • Behnaz Ansari Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran and Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  • Masoud Etemadifar Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran and Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  • Mohammadreza Najafi Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran and Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  • Maryam Nasri Grovemead Health Centre, London, UK
  • Rokhsareh Meamar Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Keywords: Epilepsy, Autoantibodies, Gamma-Aminobutyric Acid Receptor, Temporal Lobe Epilepsy, Focal Epilepsy

Abstract

Background: This study was designed to investigate the difference in the prevalence of neuronal autoantibodies in patients diagnosed with established temporal lobe epilepsy (TLE) of unknown cause with mesial temporal sclerosis (MTS) and patients with TLE without MTS.

Methods: In an observational cohort study design, we included thirty-three consecutive adult patients and divided them into two groups with and without MTS. We evaluated anti-neuronal and nuclear antibodies with immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA), respectively.

Results: From the thirty-three consecutive patients with epilepsy 17 (51.1%) had MTS of which 12 had unilateral and 5 had bilateral MTS. No significant difference was detected between seropositive and seronegative patients in MTS versus non-MTS groups. The studied autoantibodies were present in 16 patients, including gamma-aminobutyric acid receptor (GABA-R) antibodies being the most common in 11 (33.3%), followed by N-methyl-D-aspartate receptor (NMDA-R) in 2 (6.1%), glutamic acid decarboxylase receptor (GAD-R) in 1 (3.0%), anti-phospholipid (APL) antibody in 1 (3.0%), CV2 in 1 (3.0%), Tr in 1 (3.0%), recoverin in 1 (3.0%), and double-stranded deoxyribonucleic acid (dsDNA) antibody in 1 (3.0%) of our patients with focal epilepsy. In both MTS and non-MTS groups, eight patients were positive for antibodies; four patients were positive for GABA in the MTS group and seven for GABA in the non-MTS group.

Conclusion: Neuronal antibodies were presented in half of patients with focal epilepsy, GABA antibody being the leading one. No specific magnetic resonance imaging (MRI) findings were found in the seropositive group. Our results suggest that screening for relevant antibodies may enable us to offer a possible treatment to this group of patients.

References

1. Kroll-Seger J, Bien CG, Huppertz HJ. Non-paraneoplastic limbic encephalitis associated with antibodies to potassium channels leading to bilateral hippocampal sclerosis in a pre-pubertal girl. Epileptic Disord 2009; 11(1): 54-9.
2. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010; 51(4): 676-85.
3. Brodie MJ, Barry SJ, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology 2012; 78(20): 1548-54.
4. Khurana DS. Focal epilepsies: Immunologic and inflammatory mechanisms. Semin Pediatr Neurol 2014; 21(3): 207-13.
5. Quek AM, Britton JW, McKeon A, So E, Lennon VA, Shin C, et al. Autoimmune epilepsy: Clinical characteristics and response to immunotherapy. Arch Neurol 2012; 69(5): 582-93.
6. Bien CG, Elger CE. Limbic encephalitis: A cause of temporal lobe epilepsy with onset in adult life. Epilepsy Behav 2007; 10(4): 529-38.
7. Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011; 77(2): 179-89.
8. Moscato EH, Jain A, Peng X, Hughes EG, Dalmau J, Balice-Gordon RJ. Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: Insights from molecular, cellular and synaptic studies. Eur J Neurosci 2010; 32(2): 298-309.
9. Brenner T, Sills GJ, Hart Y, Howell S, Waters P, Brodie MJ, et al. Prevalence of neurologic autoantibodies in cohorts of patients with new and established epilepsy. Epilepsia 2013; 54(6): 1028-35.
10. Majoie HJ, de Baets M, Renier W, Lang B, Vincent A. Antibodies to voltage-gated potassium and calcium channels in epilepsy. Epilepsy Res 2006; 71(2-3): 135-41.
11. McKnight K, Jiang Y, Hart Y, Cavey A, Wroe S, Blank M, et al. Serum antibodies in epilepsy and seizure-associated disorders. Neurology 2005; 65(11): 1730-6.
12. Liimatainen S, Peltola M, Sabater L, Fallah M, Kharazmi E, Haapala AM, et al. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia 2010; 51(5): 760-7.
13. Kotsenas AL, Watson RE, Pittock SJ, Britton JW, Hoye SL, Quek AM, et al. MRI findings in autoimmune voltage-gated potassium channel complex encephalitis with seizures: One potential etiology for mesial temporal sclerosis. AJNR Am J Neuroradiol 2014; 35(1): 84-9.
14. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1981; 22(4): 489-501.
15. Blume WT, Luders HO, Mizrahi E, Tassinari C, van Emde Boas W, Engel J Jr. Glossary of descriptive terminology for ictal semiology: Report of the ILAE task force on classification and terminology. Epilepsia 2001; 42(9): 1212-8.
16. Garcia PA, Laxer KD, Barbaro NM, Dillon WP. Prognostic value of qualitative magnetic resonance imaging hippocampal abnormalities in patients undergoing temporal lobectomy for medically refractory seizures. Epilepsia 1994; 35(3): 520-4.
17. Berkovic SF, Andermann F, Olivier A, Ethier R, Melanson D, Robitaille Y, et al. Hippocampal sclerosis in temporal lobe epilepsy demonstrated by magnetic resonance imaging. Ann Neurol 1991; 29(2): 175-82.
18. Ekizoglu E, Tuzun E, Woodhall M, Lang B, Jacobson L, Icoz S, et al. Investigation of neuronal autoantibodies in two different focal epilepsy syndromes. Epilepsia 2014; 55(3): 414-22.
19. Errichiello L, Perruolo G, Pascarella A, Formisano P, Minetti C, Striano S, et al. Autoantibodies to glutamic acid decarboxylase (GAD) in focal and generalized epilepsy: A study on 233 patients. J Neuroimmunol 2009; 211(1-2): 120-3.
20. Irani SR, Bien CG, Lang B. Autoimmune epilepsies. Curr Opin Neurol 2011; 24(2): 146-53.
21. Bien CG, Holtkamp M. "Autoimmune epilepsy: Encephalitis with autoantibodies for epileptologists. Epilepsy currents 2017; 17(3): 134-41.
22. Gozubatik-Celik G, Ozkara C, Ulusoy C, Gunduz A, Delil S, Yeni N, et al. Anti-neuronal autoantibodies in both drug responsive and resistant focal seizures with unknown cause. Epilepsy Res 2017; 135: 131-6.
23. Lancaster E, Lai M, Peng X, Hughes E, Constantinescu R, Raizer J, et al. Antibodies to the GABA (B) receptor in limbic encephalitis with seizures: Case series and characterisation of the antigen. Lancet Neurol 2010; 9(1): 67-76.
24. Lai M, Hughes EG, Peng X, Zhou L, Gleichman AJ, Shu H, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009; 65(4): 424-34.
25. Petit-Pedrol M, Armangue T, Peng X, Bataller L, Cellucci T, Davis R, et al. Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: A case series, characterisation of the antigen, and analysis of the effects of antibodies. Lancet Neurol 2014; 13(3): 276-86.
26. Bettler B, Kaupmann K, Mosbacher J, Gassmann M. Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev 2004; 84(3): 835-67.
27. Hoftberger R, Titulaer MJ, Sabater L, Dome B, Rozsas A, Hegedus B, et al. Encephalitis and GABAB receptor antibodies: Novel findings in a new case series of 20 patients. Neurology 2013; 81(17): 1500-6.
28. Borusiak P, Bettendorf U, Wiegand G, Bast T, Kluger G, Philippi H, et al. Autoantibodies to neuronal antigens in children with focal epilepsy and no prima facie signs of encephalitis. Eur J Paediatr Neurol 2016; 20(4): 573-9.
29. Baysal-Kirac L, Tuzun E, Altindag E, Ekizoglu E, Kinay D, Bilgic B, et al. Are There Any Specific EEG Findings in Autoimmune Epilepsies? Clin EEG Neurosci 2016; 47(3): 224-34.
30. Niehusmann P, Dalmau J, Rudlowski C, Vincent A, Elger CE, Rossi JE, et al. Diagnostic value of N-methyl-D-aspartate receptor antibodies in women with new-onset epilepsy. Arch Neurol 2009; 66(4): 458-64.
31. Barajas RF, Collins DE, Cha S, Geschwind MD. Adult-onset drug-refractory seizure disorder associated with anti-voltage-gated potassium-channel antibody. Epilepsia 2010; 51(3): 473-7.
32. Vincent A, Irani SR, Lang B. The growing recognition of immunotherapy-responsive seizure disorders with autoantibodies to specific neuronal proteins. Curr Opin Neurol 2010; 23(2): 144-50.
33. Armangue T, Leypoldt F, Malaga I, Raspall-Chaure M, Marti I, Nichter C, et al. Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol 2014; 75(2): 317-23.
Published
2019-02-19
How to Cite
1.
Ansari B, Etemadifar M, Najafi M, Nasri M, Meamar R. Neuronal autoantibodies in focal epilepsy with or without mesial temporal sclerosis. Iran J Neurol. 18(1):13-18.
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Original Article(s)