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DOI: 10.1055/s-0038-1660860
Autoimmune Epilepsy: The Evolving Science of Neural Autoimmunity and Its Impact on Epilepsy Management
Publikationsverlauf
Publikationsdatum:
16. Juli 2018 (online)
Abstract
Autoimmune epilepsy is increasingly recognized as a distinct clinical entity, driven in large part by the recent discovery of neural autoantibodies in patients with isolated or predominant epilepsy presentations. Detection of neural autoantibodies in high-risk epilepsy patients supports an immune-mediated cause of seizures and, if applicable, directs the search for an underlying cancer when the paraneoplastic association of the associated antibody is compelling. Early diagnosis of autoimmune epilepsy is crucial, as prompt initiation of immunosuppressive treatment increases the likelihood of achieving either seizure freedom or a substantial reduction in seizure frequency. A practical clinical approach that incorporates risk scores to guide patient selection on the basis of clinical features, neural autoantibodies, and a treatment trial of immunotherapy is suggested. Elucidating an immunological basis of epilepsy provides neurologists with wider treatment options (incorporating immune-suppressive treatment), in addition to standard antiepileptic drugs, which often improves patient outcomes.
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References
- 1 Scheffer IE, Berkovic S, Capovilla G. , et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58 (04) 512-521
- 2 Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med 2011; 365 (10) 919-926
- 3 Quek AM, Britton JW, McKeon A. , et al. Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol 2012; 69 (05) 582-593
- 4 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 (03) 473-477
- 5 Toledano M, Britton JW, McKeon A. , et al. Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology 2014; 82 (18) 1578-1586
- 6 McKeon A, Pittock SJ. Paraneoplastic encephalomyelopathies: pathology and mechanisms. Acta Neuropathol 2011; 122 (04) 381-400
- 7 Greenlee JE, Clawson SA, Hill KE. , et al. Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures. J Neuroinflammation 2014; 11: 160
- 8 Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol 2004; 56 (05) 715-719
- 9 Horta ES, Lennon VA, Lachance DH. , et al. Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res 2014; 20 (14) 3862-3869
- 10 Dubey D, Alqallaf A, Hays R. , et al. Neurological autoantibody prevalence in epilepsy of unknown etiology. JAMA Neurol 2017; 74 (04) 397-402
- 11 Dubey D, Singh J, Britton JW. , et al. Predictive models in the diagnosis and treatment of autoimmune epilepsy. Epilepsia 2017; 58 (07) 1181-1189
- 12 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): 135-141
- 13 Errichiello L, Striano S, Zara F, Striano P. Temporal lobe epilepsy and anti glutamic acid decarboxylase autoimmunity. Neurol Sci 2011; 32 (04) 547-550
- 14 Liimatainen S, Peltola M, Sabater L. , et al. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia 2010; 51 (05) 760-767
- 15 McKnight K, Jiang Y, Hart Y. , et al. Serum antibodies in epilepsy and seizure-associated disorders. Neurology 2005; 65 (11) 1730-1736
- 16 Brenner T, Sills GJ, Hart Y. , et al. Prevalence of neurologic autoantibodies in cohorts of patients with new and established epilepsy. Epilepsia 2013; 54 (06) 1028-1035
- 17 Ekizoglu E, Tuzun E, Woodhall M. , et al. Investigation of neuronal autoantibodies in two different focal epilepsy syndromes. Epilepsia 2014; 55 (03) 414-422
- 18 Suleiman J, Wright S, Gill D. , et al. Autoantibodies to neuronal antigens in children with new-onset seizures classified according to the revised ILAE organization of seizures and epilepsies. Epilepsia 2013; 54 (12) 2091-2100
- 19 Dalmau J, Gleichman AJ, Hughes EG. , et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7 (12) 1091-1098
- 20 Benarroch EE. NMDA receptors: recent insights and clinical correlations. Neurology 2011; 76 (20) 1750-1757
- 21 Granerod J, Ambrose HE, Davies NW. , et al; UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 2010; 10 (12) 835-844
- 22 Niehusmann P, Dalmau J, Rudlowski C. , et al. Diagnostic value of N-methyl-D-aspartate receptor antibodies in women with new-onset epilepsy. Arch Neurol 2009; 66 (04) 458-464
- 23 Hughes EG, Peng X, Gleichman AJ. , et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci 2010; 30 (17) 5866-5875
- 24 Moscato EH, Peng X, Jain A, Parsons TD, Dalmau J, Balice-Gordon RJ. Acute mechanisms underlying antibody effects in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2014; 76 (01) 108-119
- 25 Titulaer MJ, McCracken L, Gabilondo I. , et al. Late-onset anti-NMDA receptor encephalitis. Neurology 2013; 81 (12) 1058-1063
- 26 Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011; 10 (01) 63-74
- 27 Titulaer MJ, McCracken L, Gabilondo I. , et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013; 12 (02) 157-165
- 28 Bayreuther C, Bourg V, Dellamonica J, Borg M, Bernardin G, Thomas P. Complex partial status epilepticus revealing anti-NMDA receptor encephalitis. Epileptic Disord 2009; 11 (03) 261-265
- 29 Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J, Friedman D. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 2012; 79 (11) 1094-1100
- 30 Thieben MJ, Lennon VA, Boeve BF, Aksamit AJ, Keegan M, Vernino S. Potentially reversible autoimmune limbic encephalitis with neuronal potassium channel antibody. Neurology 2004; 62 (07) 1177-1182
- 31 Irani SR, Buckley C, Vincent A. , et al. Immunotherapy-responsive seizure-like episodes with potassium channel antibodies. Neurology 2008; 71 (20) 1647-1648
- 32 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 (08) 776-785
- 33 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 (09) 2734-2748
- 34 Lancaster E, Huijbers MG, Bar V. , et al. Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia. Ann Neurol 2011; 69 (02) 303-311
- 35 Binks SNM, Klein CJ, Waters P, Pittock SJ, Irani SR. LGI1, CASPR2 and related antibodies: a molecular evolution of the phenotypes. J Neurol Neurosurg Psychiatry 2018; 89 (05) 526-534
- 36 van Sonderen A, Thijs RD, Coenders EC. , et al. Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology 2016; 87 (14) 1449-1456
- 37 van Sonderen A, Ariño H, Petit-Pedrol M. , et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology 2016; 87 (05) 521-528
- 38 Fukata Y, Lovero KL, Iwanaga T. , et al. Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. Proc Natl Acad Sci U S A 2010; 107 (08) 3799-3804
- 39 Kalachikov S, Evgrafov O, Ross B. , et al. Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nat Genet 2002; 30 (03) 335-341
- 40 Gu W, Brodtkorb E, Steinlein OK. LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures. Ann Neurol 2002; 52 (03) 364-367
- 41 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 Cell Biol 2003; 162 (06) 1149-1160
- 42 Poliak S, Gollan L, Martinez R. , et al. Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron 1999; 24 (04) 1037-1047
- 43 Strauss KA, Puffenberger EG, Huentelman MJ. , et al. Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2. N Engl J Med 2006; 354 (13) 1370-1377
- 44 Rodenas-Cuadrado P, Ho J, Vernes SC. Shining a light on CNTNAP2: complex functions to complex disorders. Eur J Hum Genet 2014; 22 (02) 171-178
- 45 Pinatel D, Hivert B, Boucraut J. , et al. Inhibitory axons are targeted in hippocampal cell culture by anti-Caspr2 autoantibodies associated with limbic encephalitis. Front Cell Neurosci 2015; 9: 265
- 46 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
- 47 Irani SR, Michell AW, Lang B. , et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011; 69 (05) 892-900
- 48 Irani SR, Stagg CJ, Schott JM. , et al. Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain 2013; 136 (Pt 10): 3151-3162
- 49 Aurangzeb S, Symmonds M, Knight RK, Kennett R, Wehner T, Irani SR. LGI1-antibody encephalitis is characterised by frequent, multifocal clinical and subclinical seizures. Seizure 2017; 50: 14-17
- 50 Andrade DM, Tai P, Dalmau J, Wennberg R. Tonic seizures: a diagnostic clue of anti-LGI1 encephalitis?. Neurology 2011; 76 (15) 1355-1357
- 51 Rocamora R, Becerra JL, Fossas P. , et al. Pilomotor seizures: an autonomic semiology of limbic encephalitis?. Seizure 2014; 23 (08) 670-673
- 52 Kotsenas AL, Watson RE, Pittock SJ. , 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 (01) 84-89
- 53 Sunwoo JS, Lee ST, Byun JI. , et al. Clinical manifestations of patients with CASPR2 antibodies. J Neuroimmunol 2015; 281: 17-22
- 54 Joubert B, Saint-Martin M, Noraz N. , et al. Characterization of a subtype of autoimmune encephalitis with anti-contactin-associated protein-like 2 antibodies in the cerebrospinal fluid, prominent limbic symptoms, and seizures. JAMA Neurol 2016; 73 (09) 1115-1124
- 55 Baysal-Kirac L, Tuzun E, Erdag E. , et al. Neuronal autoantibodies in epilepsy patients with peri-ictal autonomic findings. J Neurol 2016; 263 (03) 455-466
- 56 Benarroch EE. GABAB receptors: structure, functions, and clinical implications. Neurology 2012; 78 (08) 578-584
- 57 Lancaster E, Lai M, Peng X. , et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol 2010; 9 (01) 67-76
- 58 Boronat A, Sabater L, Saiz A, Dalmau J, Graus F. GABA(B) receptor antibodies in limbic encephalitis and anti-GAD-associated neurologic disorders. Neurology 2011; 76 (09) 795-800
- 59 Jeffery OJ, Lennon VA, Pittock SJ, Gregory JK, Britton JW, McKeon A. GABAB receptor autoantibody frequency in service serologic evaluation. Neurology 2013; 81 (10) 882-887
- 60 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
- 61 Petit-Pedrol M, Armangue T, Peng X. , 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 (03) 276-286
- 62 Spatola M, Petit-Pedrol M, Simabukuro MM. , et al. Investigations in GABAA receptor antibody-associated encephalitis. Neurology 2017; 88 (11) 1012-1020
- 63 Ohkawa T, Satake S, Yokoi N. , et al. Identification and characterization of GABA(A) receptor autoantibodies in autoimmune encephalitis. J Neurosci 2014; 34 (24) 8151-8163
- 64 Benarroch EE. GABAA receptor heterogeneity, function, and implications for epilepsy. Neurology 2007; 68 (08) 612-614
- 65 Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci 2004; 5 (07) 553-564
- 66 Zhou C, Huang Z, Ding L. , et al. Altered cortical GABAA receptor composition, physiology, and endocytosis in a mouse model of a human genetic absence epilepsy syndrome. J Biol Chem 2013; 288 (29) 21458-21472
- 67 Tanaka M, Olsen RW, Medina MT. , et al. Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy. Am J Hum Genet 2008; 82 (06) 1249-1261
- 68 Pettingill P, Kramer HB, Coebergh JA. , et al. Antibodies to GABAA receptor α1 and γ2 subunits: clinical and serologic characterization. Neurology 2015; 84 (12) 1233-1241
- 69 Lai M, Hughes EG, Peng X. , et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009; 65 (04) 424-434
- 70 Joubert B, Kerschen P, Zekeridou A. , et al. Clinical spectrum of encephalitis associated with antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor: case series and review of the literature. JAMA Neurol 2015; 72 (10) 1163-1169
- 71 Höftberger R, van Sonderen A, Leypoldt F. , et al. Encephalitis and AMPA receptor antibodies: novel findings in a case series of 22 patients. Neurology 2015; 84 (24) 2403-2412
- 72 Dogan Onugoren M, Deuretzbacher D, Haensch CA. , et al. Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series. J Neurol Neurosurg Psychiatry 2015; 86 (09) 965-972
- 73 Graus F, Boronat A, Xifró X. , et al. The expanding clinical profile of anti-AMPA receptor encephalitis. Neurology 2010; 74 (10) 857-859
- 74 Bataller L, Galiano R, García-Escrig M. , et al. Reversible paraneoplastic limbic encephalitis associated with antibodies to the AMPA receptor. Neurology 2010; 74 (03) 265-267
- 75 Saiz A, Blanco Y, Sabater L. , et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain 2008; 131 (Pt 10): 2553-2563
- 76 Malter MP, Helmstaedter C, Urbach H, Vincent A, Bien CG. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol 2010; 67 (04) 470-478
- 77 Lilleker JB, Biswas V, Mohanraj R. Glutamic acid decarboxylase (GAD) antibodies in epilepsy: diagnostic yield and therapeutic implications. Seizure 2014; 23 (08) 598-602
- 78 Pittock SJ, Yoshikawa H, Ahlskog JE. , et al. Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction. Mayo Clin Proc 2006; 81 (09) 1207-1214
- 79 Ariño H, Höftberger R, Gresa-Arribas N. , et al. Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol 2015; 72 (08) 874-881
- 80 Malter MP, Frisch C, Zeitler H. , et al. Treatment of immune-mediated temporal lobe epilepsy with GAD antibodies. Seizure 2015; 30: 57-63
- 81 Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology 1998; 50 (03) 652-657
- 82 Graus F, Keime-Guibert F, Reñe R. , et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 2001; 124 (Pt 6): 1138-1148
- 83 Rudzinski LA, Pittock SJ, McKeon A, Lennon VA, Britton JW. Extratemporal EEG and MRI findings in ANNA-1 (anti-Hu) encephalitis. Epilepsy Res 2011; 95 (03) 255-262
- 84 Jean WC, Dalmau J, Ho A, Posner JB. Analysis of the IgG subclass distribution and inflammatory infiltrates in patients with anti-Hu-associated paraneoplastic encephalomyelitis. Neurology 1994; 44 (01) 140-147
- 85 Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001; 49 (02) 146-154
- 86 Cross SA, Salomao DR, Parisi JE. , et al. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol 2003; 54 (01) 38-50
- 87 Dalmau J, Graus F, Villarejo A. , et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004; 127 (Pt 8): 1831-1844
- 88 Lichte B, Veh RW, Meyer HE, Kilimann MW. Amphiphysin, a novel protein associated with synaptic vesicles. EMBO J 1992; 11 (07) 2521-2530
- 89 Pittock SJ, Lucchinetti CF, Parisi JE. , et al. Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol 2005; 58 (01) 96-107
- 90 Toledano M, Pittock SJ. Autoimmune epilepsy. Semin Neurol 2015; 35 (03) 245-258
- 91 Feyissa AM, López Chiriboga AS, Britton JW. Antiepileptic drug therapy in patients with autoimmune epilepsy. Neurol Neuroimmunol Neuroinflamm 2017; 4 (04) e353
- 92 Herlopian A, Rosenthal ES, Chu CJ, Cole AJ, Struck AF. Extreme delta brush evolving into status epilepticus in a patient with anti-NMDA encephalitis. Epilepsy Behav Case Rep 2016; 7: 69-71
- 93 Baysal-Kirac L, Tuzun E, Altindag E. , et al. Are there any specific EEG findings in autoimmune epilepsies?. Clin EEG Neurosci 2016; 47 (03) 224-234
- 94 Dubey D, Farzal Z, Hays R, Brown LS, Vernino S. Evaluation of positive and negative predictors of seizure outcomes among patients with immune-mediated epilepsy: a meta-analysis. Ther Adv Neurol Disorder 2016; 9 (05) 369-377
- 95 McKeon A, Lennon VA. NMDAR encephalitis: which specimens, and the value of values. Lancet Neurol 2014; 13 (02) 133-135
- 96 Bien CG, Holtkamp M. “Autoimmune epilepsy”: encephalitis with autoantibodies for epileptologists. Epilepsy Curr 2017; 17 (03) 134-141
- 97 McKeon A, Pittock SJ, Lennon VA. CSF complements serum for evaluating paraneoplastic antibodies and NMO-IgG. Neurology 2011; 76 (12) 1108-1110
- 98 Bien CG. Value of autoantibodies for prediction of treatment response in patients with autoimmune epilepsy: review of the literature and suggestions for clinical management. Epilepsia 2013; 54 (Suppl. 02) 48-55
- 99 McKeon A, Apiwattanakul M, Lachance DH. , et al. Positron emission tomography-computed tomography in paraneoplastic neurologic disorders: systematic analysis and review. Arch Neurol 2010; 67 (03) 322-329