Download PDF
Klinische Neurophysiologie 2014; 45(04): 222-229
DOI: 10.1055/s-0034-1387772
Originalia
© Georg Thieme Verlag KG Stuttgart · New York

Antikörper-vermittelte Epilepsien

Antibody-mediated Epilepsies
D. Scherfeld
1   Neurologische Klinik, Universitätsklinikum Düsseldorf
,
C. G. Bien
2   Epilepsie-Zentrum Bethel, Krankenhaus Mara, Bielefeld
› Author Affiliations
Further Information

Publication History

Publication Date:
12 September 2014 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Epilepsie ist eine der verbreitetsten neurologischen Erkrankungen. In den letzten 10 Jahren konnte ein Teil der bisher unklaren und häufig pharmakoresistenten Epilepsien auf Autoantikörper gegen neuronale Oberflächenantigene der Zellmembran zurückgeführt werden. Im Gegensatz zu den klassischen onkoneuralen Antikörpern sind diese Antikörper selten mit einem Tumor assoziiert und die durch sie ausgelösten Erkrankungen sprechen besser auf eine Immuntherapie an. Zudem wird vermutet, dass die Antikörper gegen Oberflächenproteine einen direkten pathogenen Effekt besitzen. Damit eröffnen sich neue Möglichkeiten in der Behandlung der Antikörper-vermittelten Epilepsien.

Abstract

Epilepsy is one of the most common neurological disorders. In the last decade a part of the unknown and often drug-resistant epilepsies could be explained by autoantibodies directed to neuronal cell surface antigens. In contrast to the classical onconeural antibodies, these antibodies are rarely associated with tumours and the related diseases respond better to immunotherapies. Furthermore, it is believed that the antibodies directed to surface proteins have a direct pathogenic effect. New possibilities are thereby opened up in the treatment of these antibodies-mediated epilepsies.

Schlüsselwörter

Epilepsie - Antikörper - neuronale Oberflächenantigene - limbische Enzephalitis - Immuntherapie

Key words

epilepsy - antibodies - neuronal surface antigens - limbic encephalitis - immunotherapy
 

  • Literatur

  • 1 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: 144-150
    CrossrefPubMedGoogle Scholar
  • 2 Irani SR, Bien CG, Lang B. Autoimmune epilepsies. Curr Opin Neurol 2011; 24: 146-153
    CrossrefPubMedGoogle Scholar
  • 3 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
    CrossrefPubMedGoogle Scholar
  • 4 Graus F, Delattre JY, Antoine JC et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004; 75: 1135-1140
    CrossrefPubMedGoogle Scholar
  • 5 Bien CG, Vincent A, Barnett MH et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain 2012; 135: 1622-1638
    CrossrefPubMedGoogle Scholar
  • 6 Ances BM, Vitaliani R, Taylor RA et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain 2005; 128: 1764-1777
    CrossrefPubMedGoogle Scholar
  • 7 Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011; 77: 179-189
    CrossrefPubMedGoogle Scholar
  • 8 Brierley JB, Corsellis JAN, Hierons R et al. Subacute encephalitis of later adult life mainly affecting the limbic areas. Brain 1960; 83: 357-368
    CrossrefPubMedGoogle Scholar
  • 9 Corsellis JA, Goldberg GJ, Norton AR. “Limbic encephalitis” and its association with carcinoma. Brain 1968; 91: 481-496
    CrossrefPubMedGoogle Scholar
  • 10 Bien CG, Elger CE. Limbic encephalitis: a cause of temporal lobe epilepsy with onset in adult life. Epilepsy Behav 2007; 10: 529-538
    CrossrefPubMedGoogle Scholar
  • 11 Irani SR, Michell AW, Lang B et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011; 69: 892-900
    CrossrefPubMedGoogle Scholar
  • 12 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: 3151-3162
    CrossrefPubMedGoogle Scholar
  • 13 Castillo P, Woodruff B, Caselli R et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol 2006; 63: 197-202
    CrossrefPubMedGoogle Scholar
  • 14 Brain L, Jellinek EH, Ball K. Hashimoto’s disease and encephalopathy. Lancet 1966; 2: 512-514
    PubMedGoogle Scholar
  • 15 Liimatainen S, Peltola M, Sabater L et al. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia 2010; 51: 760-767
    CrossrefPubMedGoogle Scholar
  • 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: 1028-1035
    CrossrefPubMedGoogle Scholar
  • 17 Ekizoglu E, Tuzun E, Woodhall M et al. Investigation of neuronal autoantibodies in two different focal epilepsy syndromes. Epilepsia 2014; 55: 414-422
    CrossrefPubMedGoogle Scholar
  • 18 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
    CrossrefPubMedGoogle Scholar
  • 19 Dalmau J, Tüzün E, Wu HY et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61: 25-36
    Google Scholar
  • 20 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: 157-165
    CrossrefPubMedGoogle Scholar
  • 21 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: 1091-1098
    CrossrefPubMedGoogle Scholar
  • 22 Gresa-Arribas N, Titulaer MJ, Torrents A et al. Antibody titres at diag­nosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol 2014; 13: 167-177
    CrossrefPubMedGoogle Scholar
  • 23 Hughes EG, Peng X, Gleichman AJ et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci 2010; 30: 5866-5875
    CrossrefPubMedGoogle Scholar
  • 24 Davis R, Dalmau J. Autoimmunity, seizures, and status epilepticus. Epilepsia 2013; 54 (Suppl. 06) 46-49
    CrossrefPubMedGoogle Scholar
  • 25 Dalmau J, Lancaster E, Martinez-Hernandez E et al. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011; 10: 63-74
    Google Scholar
  • 26 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: 458-464
    CrossrefPubMedGoogle Scholar
  • 27 Schmitt SE, Pargeon K, Frechette ES et al. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 2012; 79: 1094-1100
    CrossrefPubMedGoogle Scholar
  • 28 Malter MP, Elger CE, Surges R. Diagnostic value of CSF findings in antibodyassociated limbic and anti-NMDAR-encephalitis. Seizure 2013; 22: 136-140
    CrossrefPubMedGoogle Scholar
  • 29 Vernino S, Lennon VA. Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability. Muscle Nerve 2002; 26: 702-707
    CrossrefPubMedGoogle Scholar
  • 30 Vincent A, Buckley C, Schott JM et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 2004; 127: 701-712
    CrossrefPubMedGoogle Scholar
  • 31 Liguori R, Vincent A, Clover L et al. Morvan’s syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain 2001; 124: 2417-2426
    CrossrefPubMedGoogle Scholar
  • 32 Irani SR, Buckley C, Vincent A et al. Immunotherapy-responsive seizure-like episodes with potassium channel antibodies. Neurology 2008; 71: 1647-1648
    CrossrefPubMedGoogle Scholar
  • 33 Geschwind MD, Tan KM, Lennon VA et al. Voltage-gated potassium channel autoimmunity mimicking creutzfeldt-jakob disease. Arch Neurol 2008; 65: 1341-1346
    CrossrefPubMedGoogle Scholar
  • 34 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: 2734-2748
    CrossrefPubMedGoogle Scholar
  • 35 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: 776-785
    CrossrefPubMedGoogle Scholar
  • 36 Wieser S, Kelemen A, Barsi P et al. Pilomotor seizures and status in non-paraneoplastic limbic encephalitis. Epileptic Disord 2005; 7: 205-211
    PubMedGoogle Scholar
  • 37 Shin YW, Lee ST, Shin JW et al. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. J Neuroimmunol 2013; 265: 75-81
    CrossrefPubMedGoogle Scholar
  • 38 Lancaster E, Huijbers MG, Bar V et al. Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia. Ann Neurol 2011; 69: 303-311
    CrossrefPubMedGoogle Scholar
  • 39 Lai M, Hughes EG, Peng X et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009; 65: 424-434
    CrossrefPubMedGoogle Scholar
  • 40 Bataller L, Galiano R, García-Escrig M et al. Reversible paraneoplastic limbic encephalitis associated with antibodies to the AMPA receptor. Neurology 2010; 74: 265-267
    CrossrefPubMedGoogle Scholar
  • 41 Graus F, Boronat A, Xifró X et al. The expanding clinical profile of anti-AMPA receptor encephalitis. Neurology 2010; 74: 857-859
    CrossrefPubMedGoogle Scholar
  • 42 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: 67-76
    CrossrefPubMedGoogle Scholar
  • 43 Boronat A, Sabater L, Saiz A et al. GABA(B) receptor antibodies in limbic encephalitis and anti-GAD-associated neurologic disorders. Neurology 2011; 76: 795-800
    CrossrefPubMedGoogle Scholar
  • 44 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: 1500-1506
    CrossrefPubMedGoogle Scholar
  • 45 Kim TJ, Lee ST, Shin JW et al. Clinical manifestations and outcomes of the treatment of patients with GABAB encephalitis. J Neuroimmunol 2014; 270: 45-50
    CrossrefPubMedGoogle Scholar
  • 46 Jeffery OJ, Lennon VA, Pittock SJ et al. GABAB receptor autoantibody frequency in service serologic evaluation. Neurology 2013; 81: 882-887
    CrossrefPubMedGoogle Scholar
  • 47 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: 276-286
    CrossrefPubMedGoogle Scholar
  • 48 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: 120-128
    CrossrefPubMedGoogle Scholar
  • 49 Balint B, Jarius S, Nagel S et al. Progressive encephalomyelitis with rigidity and myoclonus: a new variant with DPPX antibodies. Neurology 2014; 82: 1521-1528
    CrossrefPubMedGoogle Scholar
  • 50 Lancaster E, Martinez-Hernandez E, Titulaer MJ et al. Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology 2011; 77: 1698-1701
    CrossrefPubMedGoogle Scholar
  • 51 Mat A, Adler H, Merwick A et al. Ophelia syndrome with metabotropic glutamate receptor 5 antibodies in CSF. Neurology 2013; 80: 1349-1350
    CrossrefPubMedGoogle Scholar
  • 52 Carr I. The Ophelia syndrome: memory loss in Hodgkin’s disease. Lancet 1982; 1: 844-845
    PubMedGoogle Scholar
  • 53 Hutchinson M, Waters P, McHugh J et al. Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology 2008; 71: 1291-1292
    CrossrefPubMedGoogle Scholar
  • 54 Stern WM, Howard R, Chalmers RM et al. Glycine receptor antibody mediated Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM): a rare but treatable neurological syndrome. Pract Neurol 2014; 14: 123-127
    CrossrefPubMedGoogle Scholar
  • 55 De Blauwe SN, Santens P, Vanopdenbosch LJ. Anti-glycine receptor antibody mediated progressive encephalomyelitis with rigidity and myoclonus associated with breast cancer. Case Rep Neurol Med 2013; 2013: 589154
    PubMedGoogle Scholar
  • 56 Kyskan R, Chapman K, Mattman A et al. Antiglycine receptor antibody and encephalomyelitis with rigidity and myoclonus (PERM) related to small cell lung cancer. BMJ Case Rep 2013; DOI: 10.1136/bcr-2013-010027.
    PubMedGoogle Scholar
  • 57 McKeon A, Martinez-Hernandez E, Lancaster E et al. Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype. JAMA Neurol 2013; 70: 44-50
    CrossrefPubMedGoogle Scholar
  • 58 Wuerfel E, Bien CG, Vincent A et al. Glycine receptor antibodies in a boy with focal epilepsy and episodic behavioral disorder. J Neurol Sci [in press]
    PubMedGoogle Scholar
  • 59 Zuliani L, Graus F, Giometto B et al. Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition. J Neurol Neurosurg Psychiatry 2012; 83: 638-645
    CrossrefPubMedGoogle Scholar
  • 60 Quek AM, Britton JW, McKeon A et al. Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol 2012; 69: 582-593
    CrossrefPubMedGoogle Scholar
  • 61 Titulaer MJ, Soffietti R, Dalmau J et al. Screening for tumours in paraneoplastic syndromes: report of an EFNS task force. Eur J Neurol 2011; 18: 19-e3
    CrossrefPubMedGoogle Scholar
  • 62 Graus F, Vega F, Delattre JY et al. Plasmapheresis and antineoplastic treatment in CNS paraneoplastic syndromes with antineuronal autoantibodies. Neurology 1992; 42: 536-540
    CrossrefPubMedGoogle Scholar
  • 63 Ramanathan S, Wong CH, Fung VS. Long duration between presentation of probable anti-N-methyl-D-aspartate receptor encephalitis and either clinical relapse or positive serum autoantibodies. J Clin Neurosci 2013; 20: 1322-1323
    CrossrefPubMedGoogle Scholar
  • 64 Hansen HC, Klingbeil C, Dalmau J et al. Persistent intrathecal antibody synthesis 15 years after recovering from anti-N-methyl-D-aspartate receptor encephalitis. JAMA Neurol 2013; 70: 117-119
    CrossrefPubMedGoogle Scholar