Advertisement

Der Nervenarzt

, Volume 89, Issue 1, pp 99–112 | Cite as

Update Anti-N-Methyl-D-Aspartat-Rezeptor-Enzephalitis

  • S. Kovac
  • J. Alferink
  • D. Ahmetspahic
  • V. Arolt
  • N. MelzerEmail author
CME

Zusammenfassung

Autoimmunenzephalitiden sind eine Gruppe autoimmun-entzündlicher Erkrankungen der grauen und weißen Substanz des zentralen Nervensystems. Die Enzephalitis mit Autoantikörpern gegen den N‑Methyl-D-Aspartat-Rezeptor (NMDA-R) ist die häufigste autoimmune Enzephalitis. Sie manifestiert sich meist mit einer Abfolge typischer psychiatrischer und neurologischer Symptome, und ihre Therapie erfordert damit eine enge interdisziplinäre Zusammenarbeit. Der Beitrag gibt eine aktualisierte Übersicht über den derzeitigen Kenntnisstand zur Diagnostik, Pathogenese und Therapie der Anti-NMDA-R-Enzephalitis aus psychiatrischer und neurologischer Perspektive.

Schlüsselwörter

Autoantikörpervermittelte Enzephalitiden Psychiatrische Symptome Neurologische Symptome Ovarielles Teratom Herpesvirusenzephalitis 

Update on anti-N-methyl-D-aspartate receptor encephalitis

Abstract

Autoimmune encephalitis is a group of autoimmune inflammatory disorders affecting both grey and white matter of the central nervous system. Encephalitis with autoantibodies against the N‑methyl-D-aspartate receptor (NMDA-R) is the most frequent autoimmune encephalitis syndrome presenting with a characteristic sequence of psychiatric and neurological symptoms. Treatment necessitates a close interdisciplinary cooperation. This article provides an update on the current knowledge on diagnostic standards, pathogenesis, and treatment strategies for anti-NMDA-R encephalitis from psychiatric and neurological perspectives.

Keywords

Autoantibody-mediated encephalitis Psychiatric symptoms Neurological symptoms Ovarian teratoma Herpes simplex encephalitis 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

S. Kovac, J. Alferink, D. Ahmetspahic, V. Arolt und N. Melzer geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Lancaster E, Martinez-Hernandez E, Dalmau J (2011) Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 77:179–189CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Dalmau J, Tüzün E, Wu H et al (2007) Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 61:25–36CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Irani SR, Vincent A (2012) The expanding spectrum of clinically-distinctive, immunotherapy-responsive autoimmune encephalopathies. Arq Neuropsiquiatr 70:300–304CrossRefPubMedGoogle Scholar
  4. 4.
    Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA (2012) The frequency of autoimmune N‑methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 54:899–904CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Prüß H, Dalmau J, Arolt V, Wandinger K‑P (2010) Anti-NMDA-Rezeptor-Enzephalitis. Nervenarzt 81:396–408CrossRefPubMedGoogle Scholar
  6. 6.
    Titulaer MJ, McCracken L, Gabilondo I et al (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 12:157–165CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10:63–74CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Irani SR, Bera K, Waters P et al (2010) N‑methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain 133:1655–1667CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Baizabal-Carvallo JF, Stocco A, Muscal E, Jankovic J (2013) The spectrum of movement disorders in children with anti-NMDA receptor encephalitis. Mov Disord 28:543–547CrossRefPubMedGoogle Scholar
  10. 10.
    Leypoldt F, Armangue T, Dalmau J (2015) Autoimmune encephalopathies. Ann N Y Acad Sci 1338:94–114CrossRefPubMedGoogle Scholar
  11. 11.
    Hammer C, Stepniak B, Schneider A et al (2014) Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity. Mol Psychiatry 19:1143–1149CrossRefPubMedGoogle Scholar
  12. 12.
    Kirkpatrick MP, Clarke CD, Sonmezturk HH, Abou-Khalil B (2011) Rhythmic delta activity represents a form of nonconvulsive status epilepticus in anti-NMDA receptor antibody encephalitis. Epilepsy Behav 20:392–394CrossRefPubMedGoogle Scholar
  13. 13.
    Sands TT, Nash K, Tong S, Sullivan J (2015) Focal seizures in children with anti-NMDA receptor antibody encephalitis. Epilepsy Res 112:31–36CrossRefPubMedGoogle Scholar
  14. 14.
    Viaccoz A, Desestret V, Ducray F et al (2014) Clinical specificities of adult male patients with NMDA receptor antibodies encephalitis. Neurology 82:556–563CrossRefPubMedGoogle Scholar
  15. 15.
    Gascon GG, al-Jarallah AA, Okamoto E, al Ahdal M, Kessie G, Frayha H (1993) Chorea as a presentation of herpes simplex encephalitis relapse. Brain Dev 15:178–181CrossRefPubMedGoogle Scholar
  16. 16.
    Armangue T, Moris G, Cantarín-Extremera V et al (2015) Autoimmune post-herpes simplex encephalitis of adults and teenagers. Neurology 85:1736–1743CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Armangue T, Leypoldt F, Málaga I et al (2014) Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol 75:317–323CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Hacohen Y, Deiva K, Pettingill P et al (2014) N‑methyl-D-aspartate receptor antibodies in post-herpes simplex virus encephalitis neurological relapse. Mov Disord 29:90–96CrossRefPubMedGoogle Scholar
  19. 19.
    Martinez-Hernandez E, Horvath J, Shiloh-Malawsky Y, Sangha N, Martinez-Lage M, Dalmau J (2011) Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis. Neurology 77:589–593CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Camdessanché J‑P, Streichenberger N, Cavillon G et al (2011) Brain immunohistopathological study in a patient with anti-NMDAR encephalitis. Eur J Neurol 18:929–931CrossRefPubMedGoogle Scholar
  21. 21.
    Blanke ML, VanDongen AMJ (2009) Activation Mechanisms of the NMDA Receptor. In: Van Dongen AM (Hrsg) Biology of the NMDA Receptor. CRC Press Taylor & Francis, Boca Raton FLGoogle Scholar
  22. 22.
    Howes O, McCutcheon R, Stone J (2015) Glutamate and dopamine in schizophrenia: an update for the 21st century. J Psychopharmacol (oxford) 29:97–115CrossRefGoogle Scholar
  23. 23.
    Joubert B, Honnorat J (2015) Autoimmune channelopathies in paraneoplastic neurological syndromes. Biochim Biophys Acta 1848:2665–2676CrossRefPubMedGoogle Scholar
  24. 24.
    Dalmau J, Gleichman AJ, Hughes EG et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Gleichman AJ, Spruce LA, Dalmau J, Seeholzer SH, Lynch DR (2012) Anti-NMDA receptor encephalitis antibody binding is dependent on amino acid identity of a small region within the GluN1 amino terminal domain. J Neurosci 32:11082–11094CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Mikasova L, De Rossi P, Bouchet D et al (2012) Disrupted surface cross-talk between NMDA and Ephrin-B2 receptors in anti-NMDA encephalitis. Brain 135:1606–1621CrossRefPubMedGoogle Scholar
  27. 27.
    Hughes EG, Peng X, Gleichman AJ et al (2010) Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci 30:5866–5875CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Kreye J, Wenke NK, Chayka M et al (2016) Human cerebrospinal fluid monoclonal N‑methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis. Brain.  https://doi.org/10.1093/brain/aww208 Google Scholar
  29. 29.
    Planagumà J, Leypoldt F, Mannara F et al (2015) Human N‑methyl D‑aspartate receptor antibodies alter memory and behaviour in mice. Brain 138:94–109CrossRefPubMedGoogle Scholar
  30. 30.
    Kayser MS, Dalmau J (2016) Anti-NMDA receptor encephalitis, autoimmunity, and psychosis. Schizophr Res 176:36–40CrossRefPubMedGoogle Scholar
  31. 31.
    Olney JW, Newcomer JW, Farber NB (1999) NMDA receptor hypofunction model of schizophrenia. J Psychiatr Res 33:523–533CrossRefPubMedGoogle Scholar
  32. 32.
    Coyle JT (2006) Glutamate and schizophrenia: beyond the dopamine hypothesis. Cell Mol Neurobiol 26:365–384CrossRefPubMedGoogle Scholar
  33. 33.
    Schmitt A, Malchow B, Keeser D, Falkai P, Hasan A (2015) Neurobiologie der Schizophrenie. Nervenarzt 86:324–331CrossRefPubMedGoogle Scholar
  34. 34.
    Deakin J, Lennox BR, Zandi MS (2014) Antibodies to the N‑methyl-D-aspartate receptor and other synaptic proteins in psychosis. Biol Psychiatry 75:284–291CrossRefPubMedGoogle Scholar
  35. 35.
    Ezeoke A, Mellor A, Buckley P, Miller B (2013) A systematic, quantitative review of blood autoantibodies in schizophrenia. Schizophr Res 150:245–251CrossRefPubMedGoogle Scholar
  36. 36.
    Zandi MS, Irani SR, Lang B et al (2011) Disease-relevant autoantibodies in first episode schizophrenia. J Neurol 258:686–688CrossRefPubMedGoogle Scholar
  37. 37.
    Steiner J, Walter M, Glanz W et al (2013) Increased prevalence of diverse N‑methyl-D-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: specific relevance of IgG NR1a antibodies for distinction from N‑methyl-D-aspartate glutamate receptor encephalitis. JAMA Psychiatry 70:271–278CrossRefPubMedGoogle Scholar
  38. 38.
    Pollak TA, McCormack R, Peakman M, Nicholson TR, David AS (2014) Prevalence of anti-N-methyl-D-aspartate (NMDA) receptor [corrected] antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychol Med 44:2475–2487CrossRefPubMedGoogle Scholar
  39. 39.
    Dahm L, Ott C, Steiner J et al (2014) Seroprevalence of autoantibodies against brain antigens in health and disease. Ann Neurol 76:82–94CrossRefPubMedGoogle Scholar
  40. 40.
    Busse S, Busse M, Brix B et al (2014) Seroprevalence of N‑methyl-D-aspartate glutamate receptor (NMDA-R) autoantibodies in aging subjects without neuropsychiatric disorders and in dementia patients. Eur Arch Psychiatry Clin Neurosci 264:545–550CrossRefPubMedGoogle Scholar
  41. 41.
    Gresa-Arribas N, Titulaer MJ, Torrents A et al (2014) Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol 13:167–177CrossRefPubMedGoogle Scholar
  42. 42.
    Castillo-Gómez E, Oliveira B, Tapken D et al (2016) All naturally occurring autoantibodies against the NMDA receptor subunit NR1 have pathogenic potential irrespective of epitope and immunoglobulin class. Mol Psychiatry.  https://doi.org/10.1038/mp.2016.125 PubMedGoogle Scholar
  43. 43.
    Lennox BR, Palmer-Cooper EC, Pollak T et al (2017) Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study. Lancet Psychiatry 4:42–48CrossRefPubMedGoogle Scholar
  44. 44.
    Manto M, Dalmau J, Didelot A, Rogemond V, Honnorat J (2010) In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction. Orphanet J Rare Dis 5:31CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Bien CG, Vincent A, Barnett MH et al (2012) Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain 135:1622:1638Google Scholar
  46. 46.
    Graus F, Titulaer MJ, Balu R et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15:391–404CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Veciana M, Becerra JL, Fossas P et al (2015) EEG extreme delta brush: An ictal pattern in patients with anti-NMDA receptor encephalitis. Epilepsy Behav 49:280–285CrossRefPubMedGoogle Scholar
  48. 48.
    Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J, Friedman D (2012) Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 79:1094–1100CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Clancy RR, Bergqvist AGC, Dlugos DJ (2003) Neonatal Electroencephalography. Current Practice of Clinical Electroencephalography. Lippincott Williams &Wilkins, Philadelphia Baltimore, S 160–234Google Scholar
  50. 50.
    Chanson E, Bicilli É, Lauxerois M et al (2016) Anti-NMDA-R encephalitis: Should we consider extreme delta brush as electrical status epilepticus? Neurophysiol Clin 46:17–25CrossRefPubMedGoogle Scholar
  51. 51.
    Iizuka T, Yoshii S, Kan S et al (2010) Reversible brain atrophy in anti-NMDA receptor encephalitis: a long-term observational study. J Neurol 257:1686–1691CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Llorens V, Gabilondo I, Gómez-Esteban JC et al (2010) Abnormal multifocal cerebral blood flow on Tc-99m HMPAO SPECT in a patient with anti-NMDA-receptor encephalitis. J Neurol 257:1568–1569CrossRefPubMedGoogle Scholar
  53. 53.
    Prüss H, Finke C, Höltje M et al (2012) N‑methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 72:902–911CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Dogan Onugoren M, Golombeck KS, Bien C et al (2016) Immunoadsorption therapy in autoimmune encephalitides. Neurol Neuroimmunol Neuroinflamm 3:e207CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J (1988) Interobserver agreement for the assessment of handicap in stroke patients. Stroke 19:604–607CrossRefPubMedGoogle Scholar
  56. 56.
    Behrendt V, Krogias C, Reinacher-Schick A, Gold R, Kleiter I (2016) Bortezomib treatment for patients with anti-N-methyl-d-Aspartate receptor encephalitis. JAMA Neurol 73:1251–1253CrossRefPubMedGoogle Scholar
  57. 57.
    Scheibe F, Prüss H, Mengel AM et al (2017) Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology 88:366–370CrossRefPubMedGoogle Scholar
  58. 58.
    Lee W‑J, Lee S‑T, Moon J et al (2016) Tocilizumab in autoimmune encephalitis refractory to Rituximab: an institutional cohort study. Neurotherapeutics 13:824–832CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH 2017

Authors and Affiliations

  • S. Kovac
    • 1
  • J. Alferink
    • 2
    • 3
  • D. Ahmetspahic
    • 2
    • 3
  • V. Arolt
    • 2
    • 3
  • N. Melzer
    • 1
    Email author
  1. 1.Klinik für Allgemeine Neurologie mit Institut für Translationale NeurologieUniversitätsklinikum MünsterMünsterDeutschland
  2. 2.Cluster of Excellence EXC 1003, Cells in MotionUniversität MünsterMünsterDeutschland
  3. 3.Klinik für Psychiatrie und PsychotherapieUniversitätsklinikum MünsterMünsterDeutschland

Personalised recommendations