Autoimmune Encephalitis



Autoimmune encephalitis (AE) is a group of neuropsychiatric disorders with different pathophysiology. Clinically, they may present similarly as subacute onset of memory and cognition deficits followed by deterioration of mental status or coma within a few days or weeks. Even though some of the disorders have characteristic findings, it is often challenging to diagnose autoimmune encephalitis due to their similar features in clinical presentation, laboratory, and image findings. Detailed history, physical examination, specific antibody testing, as well as tests to exclude the infectious, metabolic, toxic, or other causes are often needed before the correct diagnosis can be reached. In this chapter, we will discuss about the core clinical features, diagnostic investigations, and management of the diseases. We will compare the differences between the common subtypes of the diseases.


Autoimmune encephalitis CSF Antibody Receptor 


  1. 1.
    Granerod J, Ambrose HE, Davies NW, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10(12):835–44.PubMedGoogle Scholar
  2. 2.
    Dalmau J, Lancaster E, Martinez-Hernandez E, et al. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10(1):63–74.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Irani SR, Alexander S, Waters P, et al. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain. 2010;133(9):2734–48.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Irani SR, Bera K, Waters P, et al. N-methyl-d-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain. 2010;133(Pt 6):1655–67.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Schmitt SE, Pargeon K, Frechette ES, et al. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology. 2012;79(11):1094–100.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013;12(2):157–65.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Liguori R, Vincent A, Clover L, et al. Morvan’s syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain. 2001;124(Pt 12):2417–26.PubMedGoogle Scholar
  8. 8.
    Sinha S, Newsom-Davis J, Mills K, et al. Autoimmune aetiology for acquired neuromyotonia (Isaacs’ syndrome). Lancet. 1991;338(8759):75–7.PubMedGoogle Scholar
  9. 9.
    Vincent A, Buckley C, Schott JM, et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain. 2004;127(Pt 3):701–12.PubMedGoogle Scholar
  10. 10.
    Ohkawa T, Satake S, Yokoi N, et al. Identification and characterization of GABA(A) receptor autoantibodies in autoimmune encephalitis. J Neurosci. 2014;34(24):8151–63.PubMedGoogle Scholar
  11. 11.
    Fukata Y, Adesnik H, Iwanaga T, et al. Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science. 2006;313(5794):1792–5.PubMedGoogle Scholar
  12. 12.
    Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol. 2011;69(5):892–900.PubMedGoogle Scholar
  13. 13.
    Irani SR, Pettingill P, Kleopa KA, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol. 2012;72(2):241–55.PubMedGoogle Scholar
  14. 14.
    Ismail FS, Popkirov S, Wellmer J, et al. Faciobrachio-crural dystonic seizures in LGI1 limbic encephalitis: a treatable cause of falls. Neurol Neuroimmunol Neuroinflamm. 2015;2(5):e146.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Lai M, Hughes EG, Peng X, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol. 2009;65(4):424–34.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Lai M, Huijbers MG, Lancaster E, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol. 2010;9(8):776–85.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Irani SR, Stagg CJ, Schott JM, et al. Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain. 2013;136(Pt 10):3151–62.PubMedGoogle Scholar
  18. 18.
    Shin YW, Lee ST, Shin JW, et al. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. J Neuroimmunol. 2013;265(1-2):75–81.PubMedGoogle Scholar
  19. 19.
    Vynogradova I, Savitski V, Heckmann JG. Hemichorea associated with CASPR2 antibody. Tremor Other Hyperkinet Mov (NY). 2014;4:239.Google Scholar
  20. 20.
    Spinazzi M, Argentiero V, Zuliani L, et al. Immunotherapy-reversed compulsive, monoaminergic, circadian rhythm disorder in Morvan syndrome. Neurology. 2008;71(24):2008–10.PubMedGoogle Scholar
  21. 21.
    Toosy AT, Burbridge SE, Pitkanen M, et al. Functional imaging correlates of fronto-temporal dysfunction in Morvan’s syndrome. J Neurol Neurosurg Psychiatry. 2008;79(6):734–5.PubMedGoogle Scholar
  22. 22.
    Sharma CM, Pandey RK, Kumawat BL, et al. A unique combination of autoimmune limbic encephalitis, type 1 diabetes, and Stiff person syndrome associated with GAD-65 antibody. Ann Indian Acad Neurol. 2016;19(1):146–9.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Malter MP, Helmstaedter C, Urbach H, et al. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol. 2010;67(4):470–8.PubMedGoogle Scholar
  24. 24.
    Honnorat J, Saiz A, Giometto B, et al. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol. 2001;58(2):225–30.PubMedGoogle Scholar
  25. 25.
    Hoftberger R, Titulaer MJ, Sabater L, et al. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology. 2013;81(17):1500–6.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Lau CG, Zukin RS. NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci. 2007;8(6):413–26.PubMedGoogle Scholar
  27. 27.
    Prosser HM, Gill CH, Hirst WD, et al. Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice. Mol Cell Neurosci. 2001;17(6):1059–70.PubMedGoogle Scholar
  28. 28.
    Schuler V, Luscher C, Blanchet C, et al. Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1)). Neuron. 2001;31(1):47–58.PubMedGoogle Scholar
  29. 29.
    Shepherd JD, Huganir RL. The cell biology of synaptic plasticity: AMPA receptor trafficking. Annu Rev Cell Dev Biol. 2007;23:613–43.PubMedGoogle Scholar
  30. 30.
    Lancaster E, Lai M, Peng X, et al. Antibodies to the GABA (B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol. 2010;9(1):67–76.PubMedGoogle Scholar
  31. 31.
    Kruer MC, Hoeftberger R, Lim KY, et al. Aggressive course in encephalitis with opsoclonus, ataxia, chorea, and seizures: the first pediatric case of gamma-aminobutyric acid type B receptor autoimmunity. JAMA Neurol. 2014;71(5):620–3.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Petit-Pedrol M, Armangue T, Peng X, et al. Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies. Lancet Neurol. 2014;13(3):276–86.PubMedPubMedCentralGoogle Scholar
  33. 33.
    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(46):18161–74.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Boronat A, Gelfand JM, Gresa-Arribas N, et al. Encephalitis and antibodies to dipeptidyl-peptidase-like protein-6, a subunit of Kv4.2 potassium channels. Ann Neurol. 2013;73(1):120–8.PubMedGoogle Scholar
  35. 35.
    Piepgras J, Holtje M, Michel K, et al. Anti-DPPX encephalitis: pathogenic effects of antibodies on gut and brain neurons. Neurology. 2015;85(10):890–7.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Tobin WO, Lennon VA, Komorowski L, et al. DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology. 2014;83(20):1797–803.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Dale RC, Merheb V, Pillai S, et al. Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders. Brain. 2012;135(Pt 11):3453–68.PubMedGoogle Scholar
  38. 38.
    Carvajal-Gonzalez A, Leite MI, Waters P, et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain. 2014;137(Pt 8):2178–92.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Hutchinson M, Waters P, McHugh J, et al. Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology. 2008;71(16):1291–2.PubMedGoogle Scholar
  40. 40.
    McKeon A, Robinson MT, McEvoy KM, et al. Stiff-man syndrome and variants: clinical course, treatments, and outcomes. Arch Neurol. 2012;69(2):230–8.PubMedGoogle Scholar
  41. 41.
    Wuerfel E, Bien CG, Vincent A, et al. Glycine receptor antibodies in a boy with focal epilepsy and episodic behavioral disorder. J Neurol Sci. 2014;343(1-2):180–2.PubMedGoogle Scholar
  42. 42.
    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(6):575–86.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Jian Xu
    • 1
  1. 1.Department of Neurology, Detroit Medical CenterMedical School of Wayne State UniversityDetroitUSA

Personalised recommendations