Neurological Sciences

, Volume 40, Issue 10, pp 2017–2030 | Cite as

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

  • Luigi ZulianiEmail author
  • 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
Review Article


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.


Autoimmune encephalitis NSAb NSAE NMDAR LGI1 



The authors thank Joanne Fleming for reviewing the manuscript.

Compliance with ethical standards

Conflict of interest

No competing interests have been identified.

Supplementary material

10072_2019_3930_MOESM1_ESM.docx (30 kb)
ESM 1 (DOCX 30 kb)


  1. 1.
    Dalmau J, Graus F (2018) Antibody-mediated encephalitis. N Engl J Med 378:840–851. Google Scholar
  2. 2.
    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. Google Scholar
  3. 3.
    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. Google Scholar
  4. 4.
    Sonderen A v, Coenders EC, Sanchez E et al (2016) Anti-LGI1 encephalitis. Neurology 87(14):1449–1456Google Scholar
  5. 5.
    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.
  6. 6.
    Dubey AD, Pittock SJ, Kelly CR et al (2018) Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 83(1):166–177.
  7. 7.
    Graus F, Titulaer MJ, Balu R et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15:391–404. Google Scholar
  8. 8.
    Dalmau J (2016) NMDA receptor encephalitis and other antibody-mediated disorders of the synapse. Neurology:2471–2482.
  9. 9.
    Leypoldt F, Armangue T, Dalmau J (2015) Autoimmune encephalopathies. Ann N Y Acad Sci 1338:94–114. Google Scholar
  10. 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. Google Scholar
  11. 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. Google Scholar
  12. 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. Google Scholar
  13. 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. Google Scholar
  14. 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. Google Scholar
  15. 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. Google Scholar
  16. 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. Google Scholar
  17. 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. Google Scholar
  18. 18.
    Jeffery OJ, Lennon VA, Pittock SJ et al (2013) GABAB receptor autoantibody frequency in service serologic evaluation. Neurology 81:882–887. Google Scholar
  19. 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. Google Scholar
  20. 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. Google Scholar
  21. 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. Google Scholar
  22. 22.
    Arino H, Armangué T, Petit-pedrol M et al (2016) Anti-LGI1 – associated cognitive impairment. Neurology 87(8):759–765. Google Scholar
  23. 23.
    Irani SR, Pettingill P, Kleopa KA et al (2012) Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 72:241–255. Google Scholar
  24. 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. Google Scholar
  25. 25.
    Lancaster E, Huijbers MGM, Bar V et al (2011) Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia. Ann Neurol 69:303–311. Google Scholar
  26. 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. Google Scholar
  27. 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.
  28. 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. Google Scholar
  29. 29.
    Spatola M, Petit-Pedrol M, Simabukuro MM et al (2017) Investigations in GABAAreceptor antibody-associated encephalitis. Neurology 88:1012–1020. Google Scholar
  30. 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. Google Scholar
  31. 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. Google Scholar
  32. 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. Google Scholar
  33. 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. Google Scholar
  34. 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. Google Scholar
  35. 35.
    Spatola M, Sabater L, Planagumà J et al (2018) Encephalitis with mGluR5 antibodies: symptoms and antibody effects. Neurology 90:e1964–e1972. Google Scholar
  36. 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. Google Scholar
  37. 37.
    Hutchinson M, Waters P, McHugh J et al (2008) Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology 71:1291–1292. Google Scholar
  38. 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. Google Scholar
  39. 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. Google Scholar
  40. 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. Google Scholar
  41. 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. Google Scholar
  42. 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. Google Scholar
  43. 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. Google Scholar
  44. 44.
    Gaig C, Graus F, Compta Y et al (2017) Clinical manifestations of the anti-IgLON5 disease. Neurology 88:1736–1743. Google Scholar
  45. 45.
    Irani SR, Michell AW, Lang B et al (2011) Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 69:892–900. Google Scholar
  46. 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. Google Scholar
  47. 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. Google Scholar
  48. 48.
    Graus F, Escudero D, Oleaga L et al (2018) Syndrome and outcome of antibody-negative limbic encephalitis. Eur J Neurol 25:1011–1016. Google Scholar
  49. 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. Google Scholar
  50. 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. Google Scholar
  51. 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. Google Scholar
  52. 52.
    Bradshaw MJ, Venkatesan A (2016) Herpes simplex virus-1 encephalitis in adults: pathophysiology, diagnosis, and management. Neurotherapeutics 13:493–508. Google Scholar
  53. 53.
    Tyler KL (2018) Acute viral encephalitis. N Engl J Med 379:557–566. Google Scholar
  54. 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. Google Scholar
  55. 55.
    Venkatesan A, Michael BD, Probasco JC et al (2019) Acute encephalitis in immunocompetent adults. Lancet 393:702–716. Google Scholar
  56. 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. Google Scholar
  57. 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. Google Scholar
  58. 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. Google Scholar
  59. 59.
    Lieberman JA, First MB (2018) Psychotic disorders. N Engl J Med 379:270–280. Google Scholar
  60. 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. Google Scholar
  61. 61.
    Frontera JA (2012) Metabolic encephalopathies in the critical care unit. Contin Lifelong Learn Neurol 18:611–639. Google Scholar
  62. 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. Google Scholar
  63. 63.
    Gastaldi M, Zardini E, Leante R, et al (2017) Cerebrospinal fluid analysis and the determination of oligoclonal bands. 38:217–224.
  64. 64.
    Kaplan PW, Rossetti AO (2011) EEG patterns and imaging correlations in encephalopathy: encephalopathy part II. J Clin Neurophysiol 28:233–251. Google Scholar
  65. 65.
    Spatola M, Dalmau J (2017) Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Curr Opin Neurol 30:345–353. Google Scholar
  66. 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.
  67. 67.
    Wieser H, Schindler K, Zumsteg D (2006) EEG in Creutzfeldt–Jakob disease. Clin Neurophysiol 117:935–951. Google Scholar
  68. 68.
    Wulff CH (1982) Subacute sclerosing panencephalitis: serial electroencephalographic studies. J Neurol Neurosurg Psychiatry 45:418–421. Google Scholar
  69. 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. Google Scholar
  70. 70.
    Zoccarato M, Valeggia S, Zuliani L, et al (2019) Conventional brain MRI features distinguishing limbic encephalitis from mesial temporal glioma. Neuroradiology.
  71. 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. Google Scholar
  72. 72.
    Spatola M, Petit-Pedrol M, Simabukuro MM et al (2017) Investigations in GABA A receptor antibody-associated encephalitis. Neurology. 88(11):1012–1020.
  73. 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. Google Scholar
  74. 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. Google Scholar
  75. 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. Google Scholar
  76. 76.
    Chourmouzi D, Papadopoulou E, Marias K, Drevelegas A (2014) Imaging of brain tumors. Surg Oncol Clin N Am 23:629–684. Google Scholar
  77. 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. Google Scholar
  78. 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. Google Scholar
  79. 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. Google Scholar
  80. 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. Google Scholar
  81. 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. Google Scholar
  82. 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. Google Scholar
  83. 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. Google Scholar
  84. 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. Google Scholar
  85. 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. Google Scholar
  86. 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. Google Scholar
  87. 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. Google Scholar
  88. 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. Google Scholar
  89. 89.
    McCracken L, Zhang J, Greene M et al (2017) Improving the antibody-based evaluation of autoimmune encephalitis. Neurol Neuroimmunol NeuroInflammation 4:1–7. Google Scholar
  90. 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. Google Scholar
  91. 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. Google Scholar
  92. 92.
    Mariotto S, Andreetta F, Farinazzo A et al (2017) Persistence of anti-NMDAR antibodies in CSF after recovery from autoimmune encephalitis. Neurol Sci.
  93. 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. Google Scholar
  94. 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. Google Scholar
  95. 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. Google Scholar
  96. 96.
    Zoccarato M, Gastaldi M, Zuliani L et al (2017) Diagnostics of paraneoplastic neurological syndromes. Neurol Sci 38(Suppl 2):237–242. Google Scholar
  97. 97.
    Franciotta D, Gastaldi M, Sala A, et al (2017) Diagnostics of the neuromyelitis optica spectrum disorders (NMOSD). 38:231–236. Google Scholar
  98. 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. Google Scholar
  99. 99.
    Jarius S, Paul F, Aktas O et al (2018) MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation 15:1–10. Google Scholar
  100. 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. Google Scholar
  101. 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. Google Scholar
  102. 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. Google Scholar
  103. 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. Google Scholar
  104. 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. Google Scholar
  105. 105.
    Hacohen Y, Absoud M, Hemingway C et al (2014) NMDA receptor antibodies associated with distinct white matter syndromes. Neurol Neuroimmunol neuroinflammation 1:e2. Google Scholar
  106. 106.
    Carecchio M, Zorzi G, Ragona F et al (2018) ATP1A3-related disorders: an update. Eur J Paediatr Neurol 22:257–263. Google Scholar
  107. 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. Google Scholar
  108. 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. Google Scholar
  109. 109.
    McKeon A (2013) The importance of early and sustained treatment of a common autoimmune encephalitis. Lancet Neurol 12:123–125. Google Scholar
  110. 110.
    Nosadini M, Mohammad SS, Ramanathan S et al (2015) Immune therapy in autoimmune encephalitis: a systematic review. Expert Rev Neurother 15:1391–1419. Google Scholar
  111. 111.
    Gastaldi M, Thouin A, Vincent A (2016) Antibody-mediated autoimmune encephalopathies and immunotherapies. Neurotherapeutics 13:147–162. Google Scholar
  112. 112.
    Lancaster E (2016) The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol 12(1):13. Google Scholar
  113. 113.
    Dale RC, Gorman MP, Lim M (2017) Autoimmune encephalitis in children: clinical phenomenology, therapeutics, and emerging challenges. Curr Opin Neurol 30:334–344. Google Scholar
  114. 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.
  115. 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. Google Scholar
  116. 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. Google Scholar
  117. 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. Google Scholar
  118. 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. Google Scholar
  119. 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. Google Scholar
  120. 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. Google Scholar
  121. 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. Google Scholar
  122. 122.
    Thompson J, Bi M, Murchison AG, et al (2018) The importance of early immunotherapy in patients with faciobrachial dystonic seizures. 348–356.
  123. 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. Google Scholar
  124. 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. Google Scholar
  125. 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. Google Scholar
  126. 126.
    Pittock SJ, Palace J (2016) Paraneoplastic and idiopathic autoimmune neurologic disorders: approach to diagnosis and treatment. Handb Clin Neurol 133:165–183.
  127. 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. Google Scholar
  128. 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. Google Scholar
  129. 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. Google Scholar
  130. 130.
    Lee WJ, Lee ST, Byun JI et al (2016) Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort. Neurology 86:1683–1691. Google Scholar
  131. 131.
    Scheibe F, Prüss H, Mengel AM et al (2016) Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology 88:366–379. Google Scholar
  132. 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. Google Scholar
  133. 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. Google Scholar
  134. 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. Google Scholar
  135. 135.
    Jun J, Lee S, Kim R et al (2018) Tocilizumab treatment for new-onset refractory status epilepticus. Ann Neurol 84:940–945. Google Scholar
  136. 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.
  137. 137.
    Finke C, Kopp UA, Prüss H et al (2012) Cognitive deficits following anti-NMDA receptor encephalitis. J Neurol Neurosurg Psychiatry 83:195–198. Google Scholar
  138. 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. Google Scholar
  139. 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. Google Scholar
  140. 140.
    Gabilondo I, Saiz A, Galán L et al (2011) Analysis of relapses in anti-NMDAR encephalitis. Neurology 77:996–999. Google Scholar

Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  • Luigi Zuliani
    • 1
    • 2
    Email author
  • Margherita Nosadini
    • 3
    • 2
  • Matteo Gastaldi
    • 4
  • Marianna Spatola
    • 5
  • Raffaele Iorio
    • 6
  • Marco Zoccarato
    • 7
    • 2
  • Sara Mariotto
    • 8
  • Piera De Gaspari
    • 2
  • Francesco Perini
    • 1
  • Sergio Ferrari
    • 8
  • Amelia Evoli
    • 6
  • Stefano Sartori
    • 3
    • 2
  • Diego Franciotta
    • 4
  • Bruno Giometto
    • 9
  1. 1.Department of NeurologyOspedale San BortoloVicenzaItaly
  2. 2.Neuroimmunology Group, Pediatric Research Institute “Città della Speranza”PadovaItaly
  3. 3.Department of Women’s and Children’s Health, Paediatric Neurology and Neurophysiology UnitUniversity Hospital of PaduaPaduaItaly
  4. 4.Neuroimmunology LaboratoryIRCCS Mondino FoundationPaviaItaly
  5. 5.Institut d’Investigacions Biomediques August Pi i Sunyer, Hospital ClınicUniversity of BarcelonaBarcelonaSpain
  6. 6.Department of Neuroscience, Fondazione Policlinico Universitario ‘A.Gemelli’ IRCCSUniversità Cattolica del Sacro CuoreRomeItaly
  7. 7.Deparment of NeurologyAzienda ULSS EuganeaPaduaItaly
  8. 8.Department of Neurological, Biomedical and Movement SciencesUniversity of VeronaVeronaItaly
  9. 9.Department of NeurologyOspedale Santa ChiaraTrentoItaly

Personalised recommendations