Polymorphism of autoimmune encephalitis

Cover Page

Abstract

This review analyses the current understanding and diagnostic approaches to the management of patients with autoimmune encephalitis. Cellular and synaptic targets, involved in the pathological process in autoimmune encephalitis, are described. The presence of clinical and immunological differences in the pathology is emphasized: on the one hand, non-structural damage to the nervous system is combined with the subacute development of cognitive impairment, epileptic and psychopathological syndromes, which, on the other hand, are associated with polymorphic immunological heterogeneity. The algorithm for clinical and laboratory diagnosis is described, based on our own clinical observations of three patients. The first patient was diagnosed with a cross-autoimmune syndrome with a combination of Hodgkin’s lymphoma and anti-NMDA encephalitis, probably triggered by the reactivation of the Epstein–Barr virus with a fatal outcome. The second patient was diagnosed with autoimmune anti-LGI1 limbic encephalitis, and the third patient was seronegative to the available immunological antigens. The authors note the need to rethink the concept of ‘encephalitis of unknown aetiology’ and its transformation into ‘autoimmune encephalitis’ with the immunological diagnosis of three antigens (NMDA, LGI1, CASPR2). Considering the rarity of the disease, the high probability of initial admission to an infectious diseases or psychiatric hospital, it is worthwhile to explore this problem more widely at various research forums and to create a comprehensive, interdisciplinary approach to the diagnosis of this disease in the Russian Federation.

About the authors

E. L. Polonskii

The Nikiforov All-Russian Centre of Emergency and Radiation Medicine, St. Petersburg

Author for correspondence.
Email: platonova@neurology.ru
Russian Federation

D. I. Skulyabin

S.M. Kirov Military Medical Academy, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

S. V. Lapin

Pavlov First Saint Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

I. V. Krasakov

The Nikiforov All-Russian Centre of Emergency and Radiation Medicine, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

O. V. Tikhomirova

The Nikiforov All-Russian Centre of Emergency and Radiation Medicine, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

V. D. Nazarov

Pavlov First Saint Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

A. N. Моshnikova

Pavlov First Saint Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

I. V. Litvinenko

S.M. Kirov Military Medical Academy, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

I. M. Slashcheva

The Nikiforov All-Russian Centre of Emergency and Radiation Medicine, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Н. Т. Маматова

The Nikiforov All-Russian Centre of Emergency and Radiation Medicine, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

N. I. Zakharova

The Nikiforov All-Russian Centre of Emergency and Radiation Medicine, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

N. A. Sokolova

The Nikiforov All-Russian Centre of Emergency and Radiation Medicine, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

A. V. Маzing

Pavlov First Saint Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

A. V. Lyamina

The Nikiforov All-Russian Centre of Emergency and Radiation Medicine, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Yu. B. Belozerova

N.P. Bekhtereva Institute of the Human Brain of the Russian Academy of Sciences, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

References

  1. Choi E.W. New therapeutic challenges in autoimmune diseases. In: J. Chan (ed.) Autoimmune Diseases: Contributing factors, specific cases of autoimmune diseases, and stem cell and other therapies. IntechOpen 2012: 253–280. doi: 10.5772/48207
  2. Ramos-Casals M., Brito-Zerón P., Kostov B. et al. Google-driven search for big data in autoimmune geoepidemiology: Analysis of 394,827 patients with systemic autoimmune diseases. Autoimmun Rev 2015; 14: 670–679. doi: 10.1016/j.autrev.2015.03.008. PMID: 25842074.
  3. Karussis D.M., Vourka-Karussis U., Lehmann D. et al. Prevention and reversal of adoptively transferred, chronic relapsing experimental autoimmune encephalomyelitis with a single high dose cytoreductive treatment followed by syngeneic bone marrow transplantation. J Clin Invest 1993; 92: 765–772. doi: 10.1172/JCI116648. PMID: 7688762.
  4. Newman M.P., Blum S., Wong R.C. et al. Autoimmune encephalitis. Intern Med J 2016; 46: 148–157. doi: 10.1111/imj.12974. PMID: 26899887.
  5. Armangue T., Leypoldt F., Dalmau J. Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Curr Opin Neurol 2014; 27: 361–368. doi: 10.1097/WCO.0000000000000087. PMID: 24792345.
  6. Somnier F.E. Autoimmune encephalitis — history & current knowledge. 2013. URL: http://pandasnetwork.org/wp-content/uploads/2018/10/autoimmune_encephalitis.pdf
  7. Granerod J., Ambrose H.E., Dawless N.W. et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 2010; 10: 835–844. doi: 10.1016/S1473-3099(10)70222-X. PMID: 20952256.
  8. Graus F., Saiz A., Dalmau J. Antibodies and neuronal autoimmune disorders of the CNS. J Neurol 2010; 257: 509–517. doi: 10.1007/s00415-009-5431-9. PMID: 20035430.
  9. Lancaster E., Martinez-Hernandez E., Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011; 77: 179–189. doi: 10.1212/WNL.0b013e318224afde. PMID: 21747075.
  10. Martinez-Martinez P., Molenaar P.C., Losen M. et al. Autoantibodies to neurotransmitter receptors and ion channels: from neuromuscular to neuropsychiatric disorders. Front Genet 2013; 4: 181. doi: 10.3389/fgene.2013.00181. PMID: 24065983.
  11. Vincent A. Developments in autoimmune channelopathies. Autoimmun Rev 2013; 12: 678–681. doi: 10.1016/j.autrev.2012.10.016. PMID: 23201922.
  12. Tyuryaeva I.I. [Tumor antigens]. Tsitologya 2008; 50(3): 189–209. (In Russ.)
  13. Eichmüller S.B., Bazhin A.V. Onconeural versus paraneoplastic antigens? Curr Med Chem 2007; 14: 2489–2494. PMID: 17979702.
  14. Giometto B., Grisold W., Vitaliani R. et al. Paraneoplastic neurologic syndrome in the PNS Euronetwork database: a European study from 20 centers. Arch Neurol 2010; 67: 330–335. doi: 10.1001/archneurol.2009.341. PMID: 20212230.
  15. Zhang H., Zhou C., Wu L. et al. Are onconeural antibodies a clinical phenomenology in paraneoplastic limbic encephalitis? Mediators Inflamm 2013; 2013: 172986. doi: 10.1155/2013/172986. PMID: 23983403.
  16. 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. doi: 10.1136/jnnp-2011-301237. PMID: 22448032.
  17. Graus F. Dalmau J. Paraneoplastic neurological syndromes. Curr Opin Neurol 2007; 20: 732–737. doi: 10.1097/WCO.0b013e3282f189dc. PMID: 17992098.
  18. Berzero G., Hacohen Y., Komorowski L. et al. Paraneoplastic cerebellar degeneration associated with anti-ITPR1 antibodies. Neurol Neuroimmunol Neuroinflamm 2017; 4: e326. doi: 10.1212/NXI.0000000000000326. PMID: 28203616.
  19. Dalmau J., Tüzün E., Wu H.Y. et al. Paraneoplastic anti–N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61: 25–36. doi: 10.1002/ana.21050. PMID: 17262855.
  20. Dalmau J. NMDA receptor encephalitis and other antibody-mediated disorders of the synapse: The 2016 Cotzias Lecture. Neurology 2016; 87: 2471–2482. doi: 10.1212/WNL.0000000000003414. PMID: 27920282.
  21. Graus F., Delattre J.Y., Antoine J.C. et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004; 75:1135–1140. doi: 10.1136/jnnp.2003.034447. PMID: 15258215.
  22. Panzer J., Dalmau J. Movement disorders in paraneoplastic and autoimmune disease. Curr Opin Neurol 2011; 24: 346–353. doi: 10.1097/WCO.0b013e328347b307. PMID: 21577108.
  23. Sutton I.J., Barnett M.H., Watson J.D. et al. Paraneoplastic brainstem encephalitis and anti-Ri antibodies. J Neurol 2002; 249: 1597–1598. PMID: 12532924.
  24. Varley J., Taylor J., Irani S.R. Autoantibody-mediated diseases of the CNS: structure, dysfunction and therapy. Neuropharmacology 2018; 132: 71–82. doi: 10.1016/j.neuropharm.2017.04.046. PMID: 28476644.
  25. Vitaliani R., Mason W., Ances B. et al. Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Ann Neurol 2005; 58: 594–604. doi: 10.1002/ana.20614. PMID: 16178029.
  26. Crisp S.J., Kullmann D.M., Vincent A. Autoimmune synaptopathies. Nat Rev Neurosci 2016; 17: 103–117. doi: 10.1038/nrn.2015.27. PMID: 26806629.
  27. 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. doi: 10.1016/S1474-4422(10)70253-2. PMID: 21163445.
  28. Machado S., Pinto A.N., Irani S.R. What should you know about limbic encephalitis? Arq Neuropsiquiatr 2012; 70: 817–822. PMID: 23060110.
  29. Lai M., Hughes E.G., Peng X. et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009; 65: 424–434. doi: 10.1002/ana.21589. PMID: 19338055.
  30. Irani S.R., Michell A.W., Lang B. et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011; 69: 892–900. doi: 10.1002/ana.22307. PMID: 21416487.
  31. Irani S.R., Vincent A. The expanding spectrum of clinically-distinctive, immunotherapy-responsive autoimmune encephalopathies. Arq Neuropsiquiatr 2012; 70: 300–304. PMID: 22510741.
  32. Boronat A., Gelfand J.M., 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. doi: 10.1002/ana.23756. PMID: 23225603.
  33. Höftberger R., Titulaer M.J., Sabater L. et al. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology 2013; 81: 1500–1506. doi: 10.1212/WNL.0b013e3182a9585f. PMID: 24068784.
  34. Petit-Pedrol М., 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. doi: 10.1016/S1474-4422(13)70299-0. PMID: 24462240.
  35. Pettingill P., Kramer H.B., Coebergh J.A. et al. Antibodies to GABAA receptor α1 and γ2 subunits: clinical and serologic characterization. Neurology 2015; 84: 1233–1241. doi: 10.1212/WNL.0000000000001326. PMID: 25636713.
  36. Lancaster E., Martinez-Hernandez E., Titulaer M.J. et al. Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology 2011; 77: 1698–1701. doi: 10.1212/WNL.0b013e3182364a44. PMID: 22013185.
  37. Probst C., Komorowski L., Graaff E. et al. Standardized test for anti-Tr/DNER in patients with paraneoplastic cerebellar degeneration. Neurol Neuroimmunol Neuroinflamm 2015; 2: e68. doi: 10.1212/NXI.0000000000000068. PMID: 25745634.
  38. Joubert B., Honnorat J. Autoimmune channelopathies in paraneoplastic neurological syndromes. Biochim Biophys Acta 2015; 1848: 2665–2676. doi: 10.1016/j.bbamem.2015.04.003. PMID: 25883091.
  39. Tretter V., Mukherjee J., Maric H.M. et al. Gephyrin, the enigmatic organizer at GABAergic synapses. Front Cell Neurosci 2012; 6: 23. doi: 10.3389/fncel.2012.00023. PMID: 22615685.
  40. Sabater L., Gaig C., Gelpi E. et al. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol 2014; 13: 575–586. doi: 10.1016/S1474-4422(14)70051-1. PMID: 24703753.
  41. Irani S.R., 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. doi: 10.1093/brain/awq213. PMID: 20663977.
  42. Gresa-Arribas N., Planagumà J., Petit-Pedrol M. et al. Human neurexin-3α antibodies associate with encephalitis and alter synapse development. Neurology 2016; 86: 2235–2242. doi: 10.1212/WNL.0000000000002775. PMID: 27170573.
  43. Fraune J., Gerlach S., Rentzsch K. et al. Multiparametric serological testing in autoimmune encephalitis using computer-aided immunofluorescence microscopy (CAIFM). Autoimmun Rev 2016; 15: 937–942. doi: 10.1016/j.autrev.2016.07.024. PMID: 27490202.
  44. Stöcker W., Saschenbrecker S., Rentzsch K. et al. [Autoantibody diagnostics in neurology using native and recombinant antigenic substrates]. Nervenarzt 2013; 84: 471–476. doi: 10.1007/s00115-012-3607-5. PMID: 23568169.
  45. Wandinger K.P., Klingbeil C., Waters P. et al. Multiparametric serological testing in autoimmune encephalitis using recombinant immunofluorescence cell substrates and EUROTIDE technology. In: Scientific presentation at the 10th Dresden Symposium on Autoantibodies. Dresden, 2011.
  46. Graus F., Titulaer M.J., Balu R. et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15: 391–404. doi: 10.1016/S1474-4422(15)00401-9. PMID: 26906964.
  47. Andersson M., Alvarez-Cermeño J., Bernardi G. et al. Cerebrospinal fluid in diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry 1994; 57: 897–902. PMID: 8057110.
  48. Schmitt S.E., Pargeon K., Frechette E.S. et al. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 2012; 79: 1094–1100. doi: 10.1212/WNL.0b013e3182698cd8. PMID: 22933737.
  49. van Sonderen A., Thijs R.D., Coenders E.C. et al. Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology 2016; 87: 1449–1456. doi: 10.1212/WNL.0000000000003173. PMID: 27590293.
  50. Zandi M.S., Irani S.R., Follows G. et al. Limbic encephalitis associated with antibodies to the NMDA receptor in Hodgkin lymphoma. Neurology 2009; 73: 2039–2040. doi: 10.1212/WNL.0b013e3181c55e9b. PMID: 19996080.
  51. Carr I. The Ophelia syndrome: memory loss in Hodgkin's disease. Lancet 1982; 1: 844–845. PMID: 6122069.
  52. Salovin A., Glanzman J., Roslin K. et al. Anti-NMDA receptor encephalitis and nonencephalitic HSV-1 infection. Neurol Neuroimmunol Neuroinflamm 2018; 5: e458. doi: 10.1212/NXI.0000000000000458. PMID: 29629396.
  53. Cohen D.A., Lopez-Chiriboga A.S., Pittock S.J. et al. Posttransplant autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm 2018; 5: e497. doi: 10.1212/NXI.0000000000000497. PMID: 30175169.
  54. Noble G.P., Lancaster E. Anti-NMDAR encephalitis in a patient with Crohn disease receiving adalimumab. Neurol Neuroimmunol Neuroinflamm 2018; 5: e476. doi: 10.1212/NXI.0000000000000476. PMID: 29988714.
  55. Ishikawa Y., Ikeda K., Murata K. et al. Ophthalmoplegia and flaccid paraplegia in a patient with anti-NMDA receptor encephalitis: a case report and literature review. Intern Med 2013; 52: 2811–2815. PMID: 24334591.
  56. Titulaer M.J., Höftberger R., Iizuka T. et al. Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2014; 75: 411–428. doi: 10.1002/ana.24117. PMID: 24700511.
  57. Veciana M., Becerra J.L., Fossas P. et al. EEG extreme delta brush: an ictal pattern in patients with anti-NMDA receptor encephalitis. Epilepsy Behav 2015; 49: 280–285. doi: 10.1016/j.yebeh.2015.04.032. PMID: 26071995.
  58. Lai M., Huijbers M.G., 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. doi: 10.1016/S1474-4422(10)70137-X. PMID: 20580615.
  59. Kegel L., Aunin E., Meijer D., Bermingham J.R. LGI proteins in the nervous system. ASN Neuro 2013; 5: 167–181. doi: 10.1042/AN20120095. PMID: 23713523.
  60. Ohkawa T., Fukata Y., Yamasaki M. et al. Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors. J Neurosci 2013; 33: 18161–18174. doi: 10.1523/JNEUROSCI.3506-13.2013. PMID: 24227725.

Statistics

Views

Abstract: 628

PDF (Russian): 525

Article Metrics

Metrics Loading ...

Dimensions

PlumX


Copyright (c) 2019 Polonskii E.L., Skulyabin D.I., Lapin S.V., Krasakov I.V., Tikhomirova O.V., Nazarov V.D., Моshnikova A.N., Litvinenko I.V., Slashcheva I.M., Маматова Н.Т., Zakharova N.I., Sokolova N.A., Маzing A.V., Lyamina A.V., Belozerova Y.B.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies