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01-10-2019 | Electroencephalography | Review Article

Management of antibody-mediated autoimmune encephalitis in adults and children: literature review and consensus-based practical recommendations

Authors: Luigi Zuliani, Margherita Nosadini, Matteo Gastaldi, Marianna Spatola, Raffaele Iorio, Marco Zoccarato, Sara Mariotto, Piera De Gaspari, Francesco Perini, Sergio Ferrari, Amelia Evoli, Stefano Sartori, Diego Franciotta, Bruno Giometto

Published in: Neurological Sciences | Issue 10/2019

Abstract

Autoimmune encephalitis associated with antibodies against neuronal surface targets (NSAE) are rare but still underrecognized conditions that affect adult and pediatric patients. Clinical guidelines have recently been published with the aim of providing diagnostic clues regardless of antibody status. These syndromes are potentially treatable but the choice of treatment and its timing, as well as differential diagnoses, long-term management, and clinical and paraclinical follow-up, remain major challenges. In the absence of evidence-based guidelines, management of these conditions is commonly based on single-center expertise.

Taking into account different published expert recommendations in addition to the multicenter experience of the Italian Working Group on Autoimmune Encephalitis, both widely accepted and critical aspects of diagnosis, management and particularly of immunotherapy for NSAE have been reviewed and are discussed.

Finally, we provide consensus-based practical advice for managing hospitalization and follow-up of patients with NSAE.

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Dalmau J, Graus F (2018) Antibody-mediated encephalitis. N Engl J Med 378:840–851. https://doi.org/10.1056/NEJMra1708712 CrossRefPubMed

Zuliani L, Graus F, Giometto B et al (2012) Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition. J Neurol Neurosurg Psychiatry 83:638–645. https://doi.org/10.1136/jnnp-2011-301237 CrossRefPubMed

Granerod J, Ambrose HE, Davies NWS et al (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10:835–844. https://doi.org/10.1016/S1473-3099(10)70222-X CrossRefPubMed

Sonderen A v, Coenders EC, Sanchez E et al (2016) Anti-LGI1 encephalitis. Neurology 87(14):1449–1456CrossRefPubMed

Binks SNM, Klein CJ, Waters P et al (2017) LGI1, CASPR2 and related antibodies: a molecular evolution of the phenotypes. J Neurol Neurosurg Psychiatry 1–9. https://doi.org/10.1136/jnnp-2017-315720

Dubey AD, Pittock SJ, Kelly CR et al (2018) Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 83(1):166–177. https://doi.org/10.1002/ana.25131

Graus F, Titulaer MJ, Balu R et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15:391–404. https://doi.org/10.1016/S1474-4422(15)00401-9 CrossRefPubMedPubMedCentral

Dalmau J (2016) NMDA receptor encephalitis and other antibody-mediated disorders of the synapse. Neurology:2471–2482. https://doi.org/10.1212/WNL.0000000000003414

Leypoldt F, Armangue T, Dalmau J (2015) Autoimmune encephalopathies. Ann N Y Acad Sci 1338:94–114. https://doi.org/10.1111/nyas.12553 CrossRefPubMed

10.

Dalmau J, Gleichman AJ, Hughes EG et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098. https://doi.org/10.1016/S1474-4422(08)70224-2 CrossRefPubMedPubMedCentral

11.

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 12:157–165. https://doi.org/10.1016/S1474-4422(12)70310-1 CrossRefPubMedPubMedCentral

12.

Florance NR, Davis RL, Lam C et al (2009) Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 66:11–18. https://doi.org/10.1002/ana.21756 CrossRefPubMedPubMedCentral

13.

Dalmau J, Tüzün E, Wu HY et al (2007) Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 61:25–36. https://doi.org/10.1002/ana.21050 CrossRefPubMedPubMedCentral

14.

Höftberger R, van Sonderen A, Leypoldt F et al (2015) Encephalitis and AMPA receptor antibodies: novel findings in a case series of 22 patients. Neurology 84:2403–2412. https://doi.org/10.1212/WNL.0000000000001682 CrossRefPubMedPubMedCentral

15.

Lai M, Hughes EG, Peng X et al (2009) AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 65:424–434. https://doi.org/10.1002/ana.21589 CrossRefPubMedPubMedCentral

16.

Lancaster E, Lai M, Peng X et al (2010) Antibodies to the GABAB receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol 9:67–76. https://doi.org/10.1016/S1474-4422(09)70324-2 CrossRefPubMed

17.

Höftberger R, Titulaer MJ, Sabater L et al (2013) Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology 81:1500–1506. https://doi.org/10.1212/WNL.0b013e3182a9585f CrossRefPubMedPubMedCentral

18.

Jeffery OJ, Lennon VA, Pittock SJ et al (2013) GABAB receptor autoantibody frequency in service serologic evaluation. Neurology 81:882–887. https://doi.org/10.1212/WNL.0b013e3182a35271 CrossRefPubMedPubMedCentral

19.

Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, Peles E, Buckley C, Lang B, Vincent A (2010) 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 133:2734–2748. https://doi.org/10.1093/brain/awq213 CrossRefPubMedPubMedCentral

20.

Lai M, Huijbers MGM, Lancaster E et al (2010) Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 9:1–10. https://doi.org/10.1016/S1474-4422(10)70137-X CrossRef

21.

Van Sonderen A, Thijs RD, Coenders EC et al (2016) Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology 87:1449–1456. https://doi.org/10.1212/WNL.0000000000003173 CrossRefPubMed

22.

Arino H, Armangué T, Petit-pedrol M et al (2016) Anti-LGI1 – associated cognitive impairment. Neurology 87(8):759–765. https://doi.org/10.1212/WNL.0000000000003009 CrossRefPubMedPubMedCentral

23.

Irani SR, Pettingill P, Kleopa KA et al (2012) Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 72:241–255. https://doi.org/10.1002/ana.23577 CrossRefPubMed

24.

Becker EBE, Zuliani L, Pettingill R et al (2012) Contactin-associated protein-2 antibodies in non-paraneoplastic cerebellar ataxia. J Neurol Neurosurg Psychiatry 83:437–440. https://doi.org/10.1136/jnnp-2011-301506 CrossRefPubMed

25.

Lancaster E, Huijbers MGM, Bar V et al (2011) Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia. Ann Neurol 69:303–311. https://doi.org/10.1002/ana.22297 CrossRefPubMedPubMedCentral

26.

Joubert B, Saint-Martin M, Noraz N et al (2016) 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 73:1115–1124. https://doi.org/10.1001/jamaneurol.2016.1585 CrossRefPubMed

27.

Sonderen A Van, Ariño H, Petit-pedrol M, et al (2016) The clinical spectrum of Caspr2 antibody – associated disease. Neurology 87(5):521–528. https://doi.org/10.1212/WNL

28.

Petit-Pedrol M, Armangue T, Peng X et al (2014) 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 13:276–286. https://doi.org/10.1016/S1474-4422(13)70299-0 CrossRefPubMedPubMedCentral

29.

Spatola M, Petit-Pedrol M, Simabukuro MM et al (2017) Investigations in GABAAreceptor antibody-associated encephalitis. Neurology 88:1012–1020. https://doi.org/10.1212/WNL.0000000000003713 CrossRefPubMedPubMedCentral

30.

Boronat A, Gelfand JM, Gresa-Arribas N et al (2013) Encephalitis and antibodies to dipeptidyl-peptidase-like protein-6, a subunit of Kv4.2 potassium channels. Ann Neurol 73:120–128. https://doi.org/10.1002/ana.23756 CrossRefPubMed

31.

Tobin WO, Lennon VA, Komorowski L et al (2014) DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology 83:1797–1803. https://doi.org/10.1212/WNL.0000000000000991 CrossRefPubMedPubMedCentral

32.

Balint B, Jarius S, Nagel S et al (2014) Progressive encephalomyelitis with rigidity and myoclonus: a new variant with DPPX antibodies. Neurology 82:1521–1528. https://doi.org/10.1212/WNL.0000000000000372 CrossRefPubMed

33.

Dale RC, Merheb V, Pillai S et al (2012) Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders. Brain 135:3453–3468. https://doi.org/10.1093/brain/aws256 CrossRefPubMed

34.

Lancaster E, Martinez-Hernandez E, Titulaer MJ et al (2011) Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology 77:1698–1701. https://doi.org/10.1212/WNL.0b013e3182364a44 CrossRefPubMedPubMedCentral

35.

Spatola M, Sabater L, Planagumà J et al (2018) Encephalitis with mGluR5 antibodies: symptoms and antibody effects. Neurology 90:e1964–e1972. https://doi.org/10.1212/WNL.0000000000005614 CrossRefPubMedPubMedCentral

36.

Gresa-Arribas N, Planagumà J, Petit-Pedrol M et al (2016) Human neurexin-3α antibodies associate with encephalitis and alter synapse development. Neurology 86:2235–2242. https://doi.org/10.1212/WNL.0000000000002775 CrossRefPubMedPubMedCentral

37.

Hutchinson M, Waters P, McHugh J et al (2008) Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology 71:1291–1292. https://doi.org/10.1212/01.wnl.0000327606.50322.f0 CrossRefPubMed

38.

McKeon A, Martinez-Hernandez E, Lancaster E et al (2013) Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype. JAMA Neurol 70:44–50. https://doi.org/10.1001/jamaneurol.2013.574 CrossRefPubMedPubMedCentral

39.

Carvajal-González A, Leite MI, Waters P et al (2014) Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain 137:2178–2192. https://doi.org/10.1093/brain/awu142 CrossRefPubMedPubMedCentral

40.

Zuliani L, Ferlazzo E, Andrigo C et al (2014) Glycine receptor antibodies in 2 cases of new, adult-onset epilepsy. Neurol Neuroimmunol Neuroinflammation 1:e16. https://doi.org/10.1212/NXI.0000000000000016 CrossRef

41.

van Sonderen A, Roelen DL, Stoop JA, et al (2017) Anti-LGI1 encephalitis is strongly associated with HLA-DR7 and HLA-DRB4. 81:193–198. https://doi.org/10.1002/ana.24858 CrossRef

42.

Kim TJ, Lee ST, Moon J, Sunwoo JS, Byun JI, Lim JA, Shin YW, Jun JS, Lee HS, Lee WJ, Yang AR, Choi Y, Park KI, Jung KH, Jung KY, Kim M, Lee SK, Chu K (2017) Anti-LGI1 encephalitis is associated with unique HLA subtypes. Ann Neurol 81:183–192. https://doi.org/10.1002/ana.24860 CrossRefPubMed

43.

Binks S, Varley J, Lee W, Makuch M, Elliott K, Gelfand JM, Jacob S, Leite MI, Maddison P, Chen M, Geschwind MD, Grant E, Sen A, Waters P, McCormack M, Cavalleri GL, Barnardo M, Knight JC, Irani SR (2018) Distinct HLA associations of LGI1 and CASPR2-antibody diseases. Brain 141:2263–2271. https://doi.org/10.1093/brain/awy109 CrossRefPubMedPubMedCentral

44.

Gaig C, Graus F, Compta Y et al (2017) Clinical manifestations of the anti-IgLON5 disease. Neurology 88:1736–1743. https://doi.org/10.1212/WNL.0000000000003887 CrossRefPubMedPubMedCentral

45.

Irani SR, Michell AW, Lang B et al (2011) Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 69:892–900. https://doi.org/10.1002/ana.22307 CrossRefPubMed

46.

Irani SR, Stagg CJ, Schott JM et al (2013) Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain 136:3151–3162. https://doi.org/10.1093/brain/awt212 CrossRefPubMed

47.

Malter MP, Helmstaedter C, Urbach H et al (2010) Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol 67:470–478. https://doi.org/10.1002/ana.21917 CrossRefPubMed

48.

Graus F, Escudero D, Oleaga L et al (2018) Syndrome and outcome of antibody-negative limbic encephalitis. Eur J Neurol 25:1011–1016. https://doi.org/10.1111/ene.13661 CrossRefPubMedPubMedCentral

49.

Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, Ghezzi A, Hintzen R, Kornberg A, Pohl D, Rostasy K, Tenembaum S, Wassmer E, for the International Pediatric Multiple Sclerosis Study Group (2013) International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler 19:1261–1267. https://doi.org/10.1177/1352458513484547 CrossRefPubMed

50.

Solomon T, Michael BD, Smith PE et al (2012) Management of suspected viral encephalitis in adults - Association of British Neurologists and British Infection Association National Guidelines. J Inf Secur 64:347–373. https://doi.org/10.1016/j.jinf.2011.11.014 CrossRef

51.

Venkatesan A, Tunkel AR, Bloch KC et al (2013) Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 57:1114–1128. https://doi.org/10.1093/cid/cit458 CrossRefPubMedPubMedCentral

52.

Bradshaw MJ, Venkatesan A (2016) Herpes simplex virus-1 encephalitis in adults: pathophysiology, diagnosis, and management. Neurotherapeutics 13:493–508. https://doi.org/10.1007/s13311-016-0433-7 CrossRefPubMedPubMedCentral

53.

Tyler KL (2018) Acute viral encephalitis. N Engl J Med 379:557–566. https://doi.org/10.1016/B978-1-4377-1604-7.00422-X CrossRefPubMed

54.

Ramos-Estebanez C, Lizarraga KJ, Merenda A (2014) A systematic review on the role of adjunctive corticosteroids in herpes simplex virus encephalitis: is timing critical for safety and efficacy. Antivir Ther 19:133–139. https://doi.org/10.3851/IMP2683 CrossRefPubMed

55.

Venkatesan A, Michael BD, Probasco JC et al (2019) Acute encephalitis in immunocompetent adults. Lancet 393:702–716. https://doi.org/10.1016/S0140-6736(18)32526-1 CrossRefPubMed

56.

Armangue T, Spatola M, Vlagea A et al (2018) Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol 17:760–772. https://doi.org/10.1016/S1474-4422(18)30244-8 CrossRefPubMedPubMedCentral

57.

Nosadini M, Mohammad SS, Corazza F et al (2017) Herpes simplex virus-induced anti- N-methyl-D-aspartate receptor encephalitis: a systematic literature review with analysis of 43 cases. Dev Med Child Neurol 59:796–805. https://doi.org/10.1111/dmcn.13448 CrossRefPubMed

58.

Cavaliere E, Nosadini M, Federica M et al (2019) Anti-NMDAR encephalitis preceded by non-herpetic central nervous system infection : systematic literature review and first case of tick-borne encephalitis triggering anti-NMDAR encephalitis. J Neuroimmunol 332:1–7. https://doi.org/10.1016/j.jneuroim.2019.03.011 CrossRefPubMed

59.

Lieberman JA, First MB (2018) Psychotic disorders. N Engl J Med 379:270–280. https://doi.org/10.1056/NEJMra1801490 CrossRefPubMed

60.

Al-diwani A, Handel A, Townsend L et al (2019) The psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. Lancet Psychiatry 6:235–246. https://doi.org/10.1016/S2215-0366(19)30001-X CrossRefPubMedPubMedCentral

61.

Frontera JA (2012) Metabolic encephalopathies in the critical care unit. Contin Lifelong Learn Neurol 18:611–639. https://doi.org/10.1212/01.CON.0000415431.07019.c2 CrossRef

62.

Klein CJ, Lennon VA, Aston PA et al (2013) Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping. JAMA Neurol 70:229–234. https://doi.org/10.1001/jamaneurol.2013.592 CrossRefPubMedPubMedCentral

63.

Gastaldi M, Zardini E, Leante R, et al (2017) Cerebrospinal fluid analysis and the determination of oligoclonal bands. 38:217–224. https://doi.org/10.1007/s10072-017-3034-2

64.

Kaplan PW, Rossetti AO (2011) EEG patterns and imaging correlations in encephalopathy: encephalopathy part II. J Clin Neurophysiol 28:233–251. https://doi.org/10.1097/WNP.0b013e31821c33a0 CrossRefPubMed

65.

Spatola M, Dalmau J (2017) Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Curr Opin Neurol 30:345–353. https://doi.org/10.1097/WCO.0000000000000449 CrossRefPubMedPubMedCentral

66.

Nosadini M, Boniver C, Zuliani L et al (2015) Longitudinal electroencephalographic (EEG) findings in pediatric anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis: the Padua experience. J Child Neurol 30. https://doi.org/10.1177/0883073813515947

67.

Wieser H, Schindler K, Zumsteg D (2006) EEG in Creutzfeldt–Jakob disease. Clin Neurophysiol 117:935–951. https://doi.org/10.1016/j.clinph.2005.12.007 CrossRefPubMed

68.

Wulff CH (1982) Subacute sclerosing panencephalitis: serial electroencephalographic studies. J Neurol Neurosurg Psychiatry 45:418–421. https://doi.org/10.1136/jnnp.45.5.418 CrossRefPubMedPubMedCentral

69.

Tunkel AR, Glaser CA, Bloch KC et al (2008) The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 47:303–327. https://doi.org/10.1086/589747 CrossRefPubMed

70.

Zoccarato M, Valeggia S, Zuliani L, et al (2019) Conventional brain MRI features distinguishing limbic encephalitis from mesial temporal glioma. Neuroradiology. https://doi.org/10.1007/s00234-019-02212-1

71.

Lancaster E, Lai M, Peng X et al (2010) Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol 9:67–76. https://doi.org/10.1016/S1474-4422(09)70324-2 CrossRefPubMed

72.

Spatola M, Petit-Pedrol M, Simabukuro MM et al (2017) Investigations in GABA A receptor antibody-associated encephalitis. Neurology. 88(11):1012–1020. https://doi.org/10.1212/WNL.0000000000003713

73.

Dalmau J, Lancaster E, Martinez-Hernandez E et al (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10:63–74. https://doi.org/10.1016/S1474-4422(10)70253-2 CrossRefPubMedPubMedCentral

74.

Titulaer MJ, Höftberger R, Iizuka T et al (2014) Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 75:411–428. https://doi.org/10.1002/ana.24117 CrossRefPubMedPubMedCentral

75.

Mariotto S, Tamburin S, Salviati A et al (2014) Anti-N-methyl-D-aspartate receptor encephalitis causing a prolonged depressive disorder evolving to inflammatory brain disease. Case Rep Neurol 6:38–43. https://doi.org/10.1159/000358820 CrossRefPubMedPubMedCentral

76.

Chourmouzi D, Papadopoulou E, Marias K, Drevelegas A (2014) Imaging of brain tumors. Surg Oncol Clin N Am 23:629–684. https://doi.org/10.1016/j.soc.2014.07.004 CrossRefPubMed

77.

Baumgartner A, Rauer S, Mader I, Meyer PT (2013) Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types. J Neurol 260:2744–2753. https://doi.org/10.1007/s00415-013-7048-2 CrossRefPubMed

78.

Wegner F, Wilke F, Raab P et al (2014) Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography. BMC Neurol 14:136–147. https://doi.org/10.1186/1471-2377-14-136 CrossRefPubMedPubMedCentral

79.

Leypoldt F, Höftberger R, Titulaer MJ et al (2015) Investigations on CXCL13 in anti–N-methyl-D-aspartate receptor encephalitis. JAMA Neurol 72:180. https://doi.org/10.1001/jamaneurol.2014.2956 CrossRefPubMedPubMedCentral

80.

Probasco JC, Solnes L, Nalluri A et al (2017) Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurol - Neuroimmunol Neuroinflammation 4:e352. https://doi.org/10.1212/NXI.0000000000000352 CrossRef

81.

Ances BM, Vitaliani R, Taylor RA et al (2005) Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain 128:1764–1777. https://doi.org/10.1093/brain/awh526 CrossRefPubMed

82.

Heine J, Prüss H, Bartsch T, Ploner CJ, Paul F, Finke C (2015) Imaging of autoimmune encephalitis - relevance for clinical practice and hippocampal function. Neuroscience 309:68–83. https://doi.org/10.1016/j.neuroscience.2015.05.037 CrossRefPubMed

83.

Spatola M, Stojanova V, Prior JO et al (2014) Serial brain 18FDG-PET in anti-AMPA receptor limbic encephalitis. J Neuroimmunol 271:53–55. https://doi.org/10.1016/j.jneuroim.2014.04.002 CrossRefPubMed

84.

Park S, Choi H, Cheon GJ et al (2015) 18F-FDG PET/CT in anti-LGI1 encephalitis: initial and follow-up findings. Clin Nucl Med 40:156–158. https://doi.org/10.1097/RLU.0000000000000546 CrossRefPubMed

85.

Finke C, Kopp UA, Scheel M et al (2013) Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 74:284–296. https://doi.org/10.1002/ana.23932 CrossRefPubMed

86.

Navarro V, Kas A, Apartis E et al (2016) Motor cortex and hippocampus are the two main cortical targets in LGI1-antibody encephalitis. Brain 139:1079–1093. https://doi.org/10.1093/brain/aww012 CrossRefPubMed

87.

Kothur K, Wienholt L, Mohammad SS et al (2016) Utility of CSF cytokine/chemokines as markers of active intrathecal inflammation: comparison of demyelinating, anti-NMDAR and enteroviral encephalitis. PLoS One 11:1–19. https://doi.org/10.1371/journal.pone.0161656 CrossRef

88.

Zuliani L, Zoccarato M, Gastaldi M et al (2017) Diagnostics of autoimmune encephalitis associated with antibodies against neuronal surface antigens. Neurol Sci 38:225–229. https://doi.org/10.1007/s10072-017-3032-4 CrossRefPubMed

89.

McCracken L, Zhang J, Greene M et al (2017) Improving the antibody-based evaluation of autoimmune encephalitis. Neurol Neuroimmunol NeuroInflammation 4:1–7. https://doi.org/10.1212/NXI.0000000000000404 CrossRef

90.

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 13:167–177. https://doi.org/10.1016/S1474-4422(13)70282-5 CrossRefPubMed

91.

Gastaldi M, Thouin A, Franciotta D, Vincent A (2017) Pitfalls in the detection of N-methyl-D-aspartate-receptor (NMDA-R) antibodies. Clin Biochem 50:354–355. https://doi.org/10.1016/j.clinbiochem.2016.11.023 CrossRefPubMed

92.

Mariotto S, Andreetta F, Farinazzo A et al (2017) Persistence of anti-NMDAR antibodies in CSF after recovery from autoimmune encephalitis. Neurol Sci. https://doi.org/10.1007/s10072-017-2958-x

93.

Van Sonderen A, Schreurs MWJ, De Bruijn MAAM et al (2016) The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. Neurology 86:1692–1699. https://doi.org/10.1212/WNL.0000000000002637 CrossRefPubMed

94.

Lang B, Makuch M, Moloney T, Dettmann I, Mindorf S, Probst C, Stoecker W, Buckley C, Newton CR, Leite MI, Maddison P, Komorowski L, Adcock J, Vincent A, Waters P, Irani SR (2017) Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies. J Neurol Neurosurg Psychiatry 88:353–361. https://doi.org/10.1136/jnnp-2016-314758 CrossRefPubMed

95.

Graus F, Delattre JY, Antoine J-C et al (2004) Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 75:1135–1141. https://doi.org/10.1136/jnnp.2003.034447 CrossRefPubMedPubMedCentral

96.

Zoccarato M, Gastaldi M, Zuliani L et al (2017) Diagnostics of paraneoplastic neurological syndromes. Neurol Sci 38(Suppl 2):237–242. https://doi.org/10.1007/s10072-017-3031-5 CrossRefPubMed

97.

Franciotta D, Gastaldi M, Sala A, et al (2017) Diagnostics of the neuromyelitis optica spectrum disorders (NMOSD). 38:231–236. https://doi.org/10.1007/s10072-017-3027-1 CrossRef

98.

Mariotto S, Monaco S, Peschl P et al (2017) MOG antibody seropositivity in a patient with encephalitis: beyond the classical syndrome. BMC Neurol 17:6–11. https://doi.org/10.1186/s12883-017-0971-6 CrossRef

99.

Jarius S, Paul F, Aktas O et al (2018) MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation 15:1–10. https://doi.org/10.1186/s12974-018-1144-2 CrossRef

100.

Iorio R, Damato V, Evoli A et al (2018) Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients. J Neurol Neurosurg Psychiatry 89:138–146. https://doi.org/10.1136/jnnp-2017-316583 CrossRefPubMed

101.

Titulaer MJ, Soffietti R, Dalmau J et al (2011) Screening for tumours in paraneoplastic syndromes: report of an EFNS task force. Eur J Neurol 18:19–27. https://doi.org/10.1111/j.1468-1331.2010.03220.x CrossRefPubMed

102.

Ho ACC, Mohammad SS, Pillai SC et al (2017) High sensitivity and specificity in proposed clinical diagnostic criteria for anti-N-methyl-D-aspartate receptor encephalitis. Dev Med Child Neurol 59:1256–1260. https://doi.org/10.1111/dmcn.13579 CrossRefPubMed

103.

Hacohen Y, Wright S, Gadian J et al (2016) N-methyl-d-aspartate (NMDA) receptor antibodies encephalitis mimicking an autistic regression. Dev Med Child Neurol 58:1092–1094. https://doi.org/10.1111/dmcn.13169 CrossRefPubMed

104.

Smith JH, Dhamija R, Moseley BD, Sandroni P, Lucchinetti CF, Lennon VA, Kantarci OH (2011) N-methyl-D-aspartate receptor autoimmune encephalitis presenting with opsoclonus-myoclonus. Arch Neurol 68(8):1069–1072. https://doi.org/10.1001/archneurol.2011.166 CrossRefPubMed

105.

Hacohen Y, Absoud M, Hemingway C et al (2014) NMDA receptor antibodies associated with distinct white matter syndromes. Neurol Neuroimmunol neuroinflammation 1:e2. https://doi.org/10.1212/NXI.0000000000000002 CrossRef

106.

Carecchio M, Zorzi G, Ragona F et al (2018) ATP1A3-related disorders: an update. Eur J Paediatr Neurol 22:257–263. https://doi.org/10.1016/j.ejpn.2017.12.009 CrossRefPubMed

107.

Sartori S, Nosadini M, Cesaroni E et al (2015) Paediatric anti-N-methyl-d-aspartate receptor encephalitis: the first Italian multicenter case series. Eur J Paediatr Neurol 19:453–463. https://doi.org/10.1016/j.ejpn.2015.02.006 CrossRefPubMed

108.

Matricardi S, Patrini M, Freri E, Ragona F, Zibordi F, Andreetta F, Nardocci N, Granata T (2016) Cognitive and neuropsychological evolution in children with anti-NMDAR encephalitis. J Neurol 263:765–771. https://doi.org/10.1007/s00415-016-8056-9 CrossRefPubMed

109.

McKeon A (2013) The importance of early and sustained treatment of a common autoimmune encephalitis. Lancet Neurol 12:123–125. https://doi.org/10.1016/S1474-4422(12)70319-8 CrossRefPubMed

110.

Nosadini M, Mohammad SS, Ramanathan S et al (2015) Immune therapy in autoimmune encephalitis: a systematic review. Expert Rev Neurother 15:1391–1419. https://doi.org/10.1586/14737175.2015.1115720 CrossRefPubMed

111.

Gastaldi M, Thouin A, Vincent A (2016) Antibody-mediated autoimmune encephalopathies and immunotherapies. Neurotherapeutics 13:147–162. https://doi.org/10.1007/s13311-015-0410-6 CrossRefPubMed

112.

Lancaster E (2016) The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol 12(1):13. https://doi.org/10.3988/jcn.2016.12.1.1 CrossRef

113.

Dale RC, Gorman MP, Lim M (2017) Autoimmune encephalitis in children: clinical phenomenology, therapeutics, and emerging challenges. Curr Opin Neurol 30:334–344. https://doi.org/10.1097/WCO.0000000000000443 CrossRefPubMed

114.

Nosadini M, Mohammad SS, Suppiej A et al (2016) Intravenous immunoglobulin in paediatric neurology: safety, adherence to guidelines, and long-term outcome. Dev Med Child Neurol:1–13. https://doi.org/10.1111/dmcn.13159

115.

Gadian J, Kirk E, Holliday K et al (2017) Systematic review of immunoglobulin use in paediatric neurological and neurodevelopmental disorders. Dev Med Child Neurol 59:136–144. https://doi.org/10.1111/dmcn.13349 CrossRefPubMed

116.

Suppiej A, Nosadini M, Zuliani L, Pelizza MF, Toldo I, Bertossi C, Tison T, Zoccarato M, Marson P, Giometto B, Dale RC, Sartori S (2016) Plasma exchange in pediatric anti-NMDAR encephalitis: a systematic review. Brain and Development 38:613–622. https://doi.org/10.1016/j.braindev.2016.01.009 CrossRefPubMed

117.

Vincent A, Buckley C, Schott JM et al (2004) Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 127:701–712. https://doi.org/10.1093/brain/awh077 CrossRefPubMed

118.

Byrne S, Mccoy B, Lynch B et al (2014) Does early treatment improve outcomes in N-methyl-D-aspartate receptor encephalitis? Dev Med Child Neurol 56:794–796. https://doi.org/10.1111/dmcn.12411 CrossRefPubMed

119.

Byrne S, Lim M (2015) N-methyl-d-aspartate receptor antibody encephalitis: how much treatment is enough? Dev Med Child Neurol 57:14–15. https://doi.org/10.1111/dmcn.12559 CrossRefPubMed

120.

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 133:1655–1667. https://doi.org/10.1093/brain/awq113 CrossRefPubMedPubMedCentral

121.

Dale RC, Brilot F, Duffy LV et al (2014) Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 83:142–150. https://doi.org/10.1212/WNL.0000000000000570 CrossRefPubMedPubMedCentral

122.

Thompson J, Bi M, Murchison AG, et al (2018) The importance of early immunotherapy in patients with faciobrachial dystonic seizures. 348–356. https://doi.org/10.1093/brain/awx323

123.

Irani SR, Gelfand JM, Al-Diwani A, Vincent A (2014) Cell-surface central nervous system autoantibodies: clinical relevance and emerging paradigms. Ann Neurol 76:168–184. https://doi.org/10.1002/ana.24200 CrossRefPubMedPubMedCentral

124.

van Sonderen A, Petit-Pedrol M, Dalmau J, Titulaer MJ (2017) The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis. Nat Rev Neurol 13:290–301. https://doi.org/10.1038/nrneurol.2017.43 CrossRefPubMed

125.

Bien CG, Mirzadjanova Z, Baumgartner C et al (2017) Anti-contactin-associated protein-2 encephalitis: relevance of antibody titres, presentation and outcome. Eur J Neurol 24:175–186. https://doi.org/10.1111/ene.13180 CrossRefPubMed

126.

Pittock SJ, Palace J (2016) Paraneoplastic and idiopathic autoimmune neurologic disorders: approach to diagnosis and treatment. Handb Clin Neurol 133:165–183. https://doi.org/10.1016/B978-0-444-63432-0.00010-4

127.

Toledano M, Britton JW, McKeon A, Shin C, Lennon VA, Quek AML, So E, Worrell GA, Cascino GD, Klein CJ, Lagerlund TD, Wirrell EC, Nickels KC, Pittock SJ (2014) Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology 82:1578–1586. https://doi.org/10.1212/WNL.0000000000000383 CrossRefPubMedPubMedCentral

128.

Lim J, Lee S, Moon J et al (2019) Development of the clinical assessment scale in autoimmune encephalitis (CASE). Ann Neurol 83:352–358. https://doi.org/10.1002/ana.25421 CrossRef

129.

Dale RC, Pillai S, Brilot F (2013) Cerebrospinal fluid CD19+ B-cell expansion in N-methyl-D-aspartate receptor encephalitis. Dev Med Child Neurol 55:191–193. https://doi.org/10.1111/dmcn.12036 CrossRefPubMed

130.

Lee WJ, Lee ST, Byun JI et al (2016) Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort. Neurology 86:1683–1691. https://doi.org/10.1212/WNL.0000000000002635 CrossRefPubMed

131.

Scheibe F, Prüss H, Mengel AM et al (2016) Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology 88:366–379. https://doi.org/10.1212/WNL.0000000000003536 CrossRefPubMed

132.

Behrendt V, Krogias C, Reinacher-Schick A et al (2016) Bortezomib treatment for patients with anti-N-methyl-D-aspartate receptor encephalitis. JAMA Neurol 73:1251–1253. https://doi.org/10.1001/jamaneurol.2016.2588.jamaneurology.com CrossRefPubMed

133.

Lee WJ, Lee ST, Moon J et al (2016) Tocilizumab in autoimmune encephalitis refractory to rituximab: an institutional cohort study. Neurotherapeutics 13:824–832. https://doi.org/10.1007/s13311-016-0442-6 CrossRefPubMedPubMedCentral

134.

Tatencloux S, Chretien P, Rogemond V et al (2015) Intrathecal treatment of anti-N-methyl-d-aspartate receptor encephalitis in children. Dev Med Child Neurol 57:95–99. https://doi.org/10.1111/dmcn.12545 CrossRefPubMed

135.

Jun J, Lee S, Kim R et al (2018) Tocilizumab treatment for new-onset refractory status epilepticus. Ann Neurol 84:940–945. https://doi.org/10.1002/ana.25374 CrossRefPubMed

136.

Nosadini M, Mohammad SS, Toldo I, et al (2018) Mycophenolate mofetil, azathioprine and methotrexate usage in paediatric anti-NMDAR encephalitis: a systematic literature review. Eur J Paediatr Neurol 1–12. https://doi.org/10.1016/j.ejpn.2018.09.008

137.

Finke C, Kopp UA, Prüss H et al (2012) Cognitive deficits following anti-NMDA receptor encephalitis. J Neurol Neurosurg Psychiatry 83:195–198. https://doi.org/10.1136/jnnp-2011-300411 CrossRefPubMed

138.

Balu R, Mccracken L, Lancaster E, Graus F (2019) A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis. Neurology 92:e244–e252. https://doi.org/10.1212/WNL.0000000000006783 CrossRefPubMedPubMedCentral

139.

Finke C, Prüss H, Heine J et al (2016) Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies, pp 1–10. https://doi.org/10.1001/jamaneurol.2016.4226 CrossRef

140.

Gabilondo I, Saiz A, Galán L et al (2011) Analysis of relapses in anti-NMDAR encephalitis. Neurology 77:996–999. https://doi.org/10.1212/WNL.0b013e31822cfc6b CrossRefPubMed

Title: Management of antibody-mediated autoimmune encephalitis in adults and children: literature review and consensus-based practical recommendations
Authors: Luigi Zuliani
Margherita Nosadini
Matteo Gastaldi
Marianna Spatola
Raffaele Iorio
Marco Zoccarato
Sara Mariotto
Piera De Gaspari
Francesco Perini
Sergio Ferrari
Amelia Evoli
Stefano Sartori
Diego Franciotta
Bruno Giometto
Publication date: 01-10-2019
Publisher: Springer International Publishing
Keywords: Electroencephalography
Autoimmune Encephalitis
Encephalitis
Published in: Neurological Sciences / Issue 10/2019
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-019-03930-3

At a glance: The STEP trials

Springer Medicine

Management of antibody-mediated autoimmune encephalitis in adults and children: literature review and consensus-based practical recommendations

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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