Diagnosis and Management of Autoimmune Dementia

  • Elia Sechi
  • Eoin P. FlanaganEmail author
Dementia (J Pillai, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Dementia


Purpose of review

To describe the clinical, laboratory, and MRI features that characterize cognitive decline in the setting of central nervous system (CNS) autoimmunity, and provide an overview of current treatment modalities.

Recent findings

The field of autoimmune neurology is rapidly expanding due to the increasing number of newly discovered autoantibodies directed against specific CNS targets. The clinical syndromes associated with these autoantibodies are heterogeneous but frequently share common, recognizable clinical, and MRI characteristics. While the detection of certain autoantibodies strongly suggest the presence of an underlying malignancy (onconeural autoantibodies), a large proportion of cases remain idiopathic. Cognitive decline and encephalopathy are common manifestations of CNS autoimmunity, and can mimic neurodegenerative disorders. Recent findings suggest that the frequency of autoimmune encephalitis in the population is higher than previously thought, and potentially rivals that of infectious encephalitis. Moreover, emerging clinical scenarios that may predispose to CNS autoimmunity are increasingly been recognized. These include autoimmune dementia/encephalitis post-herpes simplex virus encephalitis, post-transplant and in association with immune checkpoint inhibitor treatment of cancer. Early recognition of autoimmune cognitive impairment is important given the potential for reversibility and disability prevention with appropriate treatment.


Autoimmune cognitive impairment is treatable and may arise in a number of different clinical settings, with important treatment implications. Several clinical and para-clinical clues may help to differentiate these disorders from dementia of other etiologies.


Autoimmune cognitive impairment Central nervous system autoimmunity Limbic encephalitis/encephalopathy Neural autoantibodies Immune check point inhibitors 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Flanagan EP, McKeon A, Lennon VA, Boeve BF, Trenerry MR, Tan KM, et al. Autoimmune dementia: clinical course and predictors of immunotherapy response. Mayo Clin Proc. 2010;85(10):881–97. Scholar
  2. 2.
    Geschwind MD, Tan KM, Lennon VA, Barajas RF Jr, Haman A, Klein CJ, et al. Voltage-gated potassium channel autoimmunity mimicking creutzfeldt-jakob disease. Arch Neurol. 2008;65(10):1341–6. Scholar
  3. 3.
    McKeon A, Marnane M, O'Connell M, Stack JP, Kelly PJ, Lynch T. Potassium channel antibody associated encephalopathy presenting with a frontotemporal dementia like syndrome. Arch Neurol. 2007;64(10):1528–30. Scholar
  4. 4.
    Mariotto S, Tamburin S, Salviati A, Ferrari S, Zoccarato M, Giometto B, et al. Anti-N-methyl-d-aspartate receptor encephalitis causing a prolonged depressive disorder evolving to inflammatory brain disease. Case Rep Neurol. 2014;6(1):38–43. Scholar
  5. 5.
    Flanagan EP, Drubach DA, Boeve BF. Autoimmune dementia and encephalopathy. Handb Clin Neurol. 2016;133:247–67. Scholar
  6. 6.
    Pittock SJ, Vincent A. Introduction to autoimmune neurology. Handb Clin Neurol. 2016;133:3–14. Scholar
  7. 7.
    Hoftberger R, van Sonderen A, Leypoldt F, Houghton D, Geschwind M, Gelfand J, et al. Encephalitis and AMPA receptor antibodies: novel findings in a case series of 22 patients. Neurology. 2015;84(24):2403–12. Scholar
  8. 8.
    Lai M, Hughes EG, Peng X, Zhou L, Gleichman AJ, Shu H, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol. 2009;65(4):424–34. Scholar
  9. 9.
    Gadoth A, Pittock SJ, Dubey D, McKeon A, Britton JW, Schmeling JE, et al. Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients. Ann Neurol. 2017;82(1):79–92. Scholar
  10. 10.
    van Sonderen A, Arino H, Petit-Pedrol M, Leypoldt F, Kortvelyessy P, Wandinger KP, et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology. 2016;87(5):521–8. Scholar
  11. 11.
    Hara M, Arino H, Petit-Pedrol M, Sabater L, Titulaer MJ, Martinez-Hernandez E, et al. DPPX antibody-associated encephalitis: Main syndrome and antibody effects. Neurology. 2017;88(14):1340–8. Scholar
  12. 12.
    Tobin WO, Lennon VA, Komorowski L, Probst C, Clardy SL, Aksamit AJ, et al. DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology. 2014;83(20):1797–803. Scholar
  13. 13.
    Spatola M, Petit-Pedrol M, Simabukuro MM, Armangue T, Castro FJ, Barcelo Artigues MI, et al. Investigations in GABAA receptor antibody-associated encephalitis. Neurology. 2017;88(11):1012–20. Scholar
  14. 14.
    Hoftberger R, Titulaer MJ, Sabater L, Dome B, Rozsas A, Hegedus B, et al. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology. 2013;81(17):1500–6. Scholar
  15. 15.
    Jeffery OJ, Lennon VA, Pittock SJ, Gregory JK, Britton JW, McKeon A. GABAB receptor autoantibody frequency in service serologic evaluation. Neurology. 2013;81(10):882–7. Scholar
  16. 16.
    Lancaster E, Lai M, Peng X, Hughes E, Constantinescu R, Raizer J, 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. Scholar
  17. 17.
    Spatola M, Sabater L, Planaguma J, Martinez-Hernandez E, Armangue T, Pruss H, et al. Encephalitis with mGluR5 antibodies: symptoms and antibody effects. Neurology. 2018;90(22):e1964–e72. Scholar
  18. 18.
    McKeon A, Martinez-Hernandez E, Lancaster E, Matsumoto JY, Harvey RJ, McEvoy KM, et al. Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype. JAMA Neurol. 2013;70(1):44–50. Scholar
  19. 19.
    Carvajal-Gonzalez A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain. 2014;137(Pt 8):2178–92. Scholar
  20. 20.
    Gaig C, Graus F, Compta Y, Hogl B, Bataller L, Bruggemann N, et al. Clinical manifestations of the anti-IgLON5 disease. Neurology. 2017;88(18):1736–43. Scholar
  21. 21.
    Honorat JA, Komorowski L, Josephs KA, Fechner K, St Louis EK, Hinson SR, et al. IgLON5 antibody: neurological accompaniments and outcomes in 20 patients. Neurol Neuroimmunol Neuroinflamm. 2017;4(5):e385. Scholar
  22. 22.
    van Sonderen A, Thijs RD, Coenders EC, Jiskoot LC, Sanchez E, de Bruijn MA, et al. Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology. 2016;87(14):1449–56. Scholar
  23. 23.
    Cobo-Calvo A, Ruiz A, Maillart E, Audoin B, Zephir H, Bourre B, et al. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology. 2018;90(21):e1858–e69. Scholar
  24. 24.
    Jurynczyk M, Messina S, Woodhall MR, Raza N, Everett R, Roca-Fernandez A, et al. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain. 2017;140(12):3128–38. Scholar
  25. 25.
    Ramanathan S, Mohammad S, Tantsis E, Nguyen TK, Merheb V, Fung VSC, et al. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry. 2018;89(2):127–37. Scholar
  26. 26.
    Gresa-Arribas N, Planaguma J, Petit-Pedrol M, Kawachi I, Katada S, Glaser CA, et al. Human neurexin-3alpha antibodies associate with encephalitis and alter synapse development. Neurology. 2016;86(24):2235–42. Scholar
  27. 27.
    Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7(12):1091–8. Scholar
  28. 28.
    Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, 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. Scholar
  29. 29.
    Do LD, Chanson E, Desestret V, Joubert B, Ducray F, Brugiere S, et al. Characteristics in limbic encephalitis with anti-adenylate kinase 5 autoantibodies. Neurology. 2017;88(6):514–24. Scholar
  30. 30.
    Pittock SJ, Lucchinetti CF, Parisi JE, Benarroch EE, Mokri B, Stephan CL, et al. Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol. 2005;58(1):96–107. Scholar
  31. 31.
    Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu--associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore). 1992;71(2):59–72.CrossRefGoogle Scholar
  32. 32.
    Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology. 1998;50(3):652–7.CrossRefGoogle Scholar
  33. 33.
    Pittock SJ, Lucchinetti CF, Lennon VA. Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol. 2003;53(5):580–7. Scholar
  34. 34.
    Honnorat J, Cartalat-Carel S, Ricard D, Camdessanche JP, Carpentier AF, Rogemond V, et al. Onco-neural antibodies and tumour type determine survival and neurological symptoms in paraneoplastic neurological syndromes with Hu or CV2/CRMP5 antibodies. J Neurol Neurosurg Psychiatry. 2009;80(4):412–6. Scholar
  35. 35.
    Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001;49(2):146–54.CrossRefGoogle Scholar
  36. 36.
    Pittock SJ, Yoshikawa H, Ahlskog JE, Tisch SH, Benarroch EE, Kryzer TJ, et al. Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction. Mayo Clin Proc. 2006;81(9):1207–14. Scholar
  37. 37.
    Saiz A, Blanco Y, Sabater L, Gonzalez F, Bataller L, Casamitjana R, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008;131(Pt 10):2553–63. Scholar
  38. 38.
    Flanagan EP, Hinson SR, Lennon VA, Fang B, Aksamit AJ, Morris PP, et al. Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: analysis of 102 patients. Ann Neurol. 2017;81(2):298–309. Scholar
  39. 39.
    Dalmau J, Graus F, Villarejo A, Posner JB, Blumenthal D, Thiessen B, et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain. 2004;127(Pt 8):1831–44. Scholar
  40. 40.
    Basal E, Zalewski N, Kryzer TJ, Hinson SR, Guo Y, Dubey D, et al. Paraneoplastic neuronal intermediate filament autoimmunity. Neurology. 2018;91(18):e1677–e89. Scholar
  41. 41.
    Vernino S, Lennon VA. New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol. 2000;47(3):297–305.CrossRefGoogle Scholar
  42. 42.••
    Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391–404. This study proposes diagnostic criteria to facilitate classification and early diagnosis and treatment of autoimmune encephalitis.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.•
    Dubey D, Pittock SJ, Kelly CR, McKeon A, Lopez-Chiriboga AS, Lennon VA, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018;83(1):166–77. This study is the first to show the population-based incidence and prevalence of autoimmune encephalitis and shows that it rivals that of infectious encephalitis.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis. 2012;54(7):899–904. Scholar
  45. 45.
    Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, 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. Scholar
  46. 46.
    Arino H, Armangue T, Petit-Pedrol M, Sabater L, Martinez-Hernandez E, Hara M, et al. Anti-LGI1-associated cognitive impairment: presentation and long-term outcome. Neurology. 2016;87(8):759–65. Scholar
  47. 47.
    Marquetand J, van Lessen M, Bender B, Reimold M, Elsen G, Stoecker W, et al. Slowly progressive LGI1 encephalitis with isolated late-onset cognitive dysfunction: a treatable mimic of Alzheimer’s disease. Eur J Neurol. 2016;23(5):e28–9. Scholar
  48. 48.
    Baumgartner A, Rauer S, Hottenrott T, Leypoldt F, Ufer F, Hegen H, et al. Admission diagnoses of patients later diagnosed with autoimmune encephalitis. J Neurol. 2018.
  49. 49.
    Lopez-Chiriboga AS, Flanagan EP. Diagnostic and therapeutic approach to autoimmune neurologic disorders. Semin Neurol. 2018;38(3):392–402. Scholar
  50. 50.
    van Sonderen A, Schreurs MW, de Bruijn MA, Boukhrissi S, Nagtzaam MM, Hulsenboom ES, et al. The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. Neurology. 2016;86(18):1692–9. Scholar
  51. 51.
    Irani SR, Michell AW, Lang B, Pettingill P, Waters P, Johnson MR, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol. 2011;69(5):892–900. Scholar
  52. 52.
    Aradillas E, Schwartzman RJ. Kinesigenic dyskinesia in a case of voltage-gated potassium channel-complex protein antibody encephalitis. Arch Neurol. 2011;68(4):529–32. Scholar
  53. 53.••
    Thompson J, Bi M, Murchison AG, Makuch M, Bien CG, Chu K, et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain. 2018;141(2):348–56. This study highlights the importance of early recognition and treatment of anti-LGI1 autoimmunity to prevent long-term cognitive impairment and disability.CrossRefPubMedGoogle Scholar
  54. 54.
    Pittock SJ, Parisi JE, McKeon A, Roemer SF, Lucchinetti CF, Tan KM, et al. Paraneoplastic jaw dystonia and laryngospasm with antineuronal nuclear autoantibody type 2 (anti-Ri). Arch Neurol. 2010;67(9):1109–15. Scholar
  55. 55.
    Boronat A, Gelfand JM, Gresa-Arribas N, Jeong HY, Walsh M, Roberts K, 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. Scholar
  56. 56.
    Sabater L, Gaig C, Gelpi E, Bataller L, Lewerenz J, Torres-Vega 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. Scholar
  57. 57.
    Oyanguren B, Sanchez V, Gonzalez FJ, de Felipe A, Esteban L, Lopez-Sendon JL, et al. Limbic encephalitis: a clinical-radiological comparison between herpetic and autoimmune etiologies. Eur J Neurol. 2013;20(12):1566–70. Scholar
  58. 58.
    Flanagan EP, Kotsenas AL, Britton JW, McKeon A, Watson RE, Klein CJ, et al. Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures. Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e161. Scholar
  59. 59.
    Kinirons P, Fulton A, Keoghan M, Brennan P, Farrell MA, Moroney JT. Paraneoplastic limbic encephalitis (PLE) and chorea associated with CRMP-5 neuronal antibody. Neurology. 2003;61(11):1623–4.CrossRefGoogle Scholar
  60. 60.
    Zhang T, Duan Y, Ye J, Xu W, Shu N, Wang C, et al. Brain MRI characteristics of patients with anti-N-methyl-D-aspartate receptor encephalitis and their associations with 2-year clinical outcome. AJNR Am J Neuroradiol. 2018;39(5):824–9. Scholar
  61. 61.
    Vitali P, Maccagnano E, Caverzasi E, Henry RG, Haman A, Torres-Chae C, et al. Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias. Neurology. 2011;76(20):1711–9. Scholar
  62. 62.
    Lopez-Chiriboga AS, Majed M, Fryer J, Dubey D, McKeon A, Flanagan EP, et al. Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG-associated disorders. JAMA Neurol. 2018;75(11):1355–63. Scholar
  63. 63.
    Sechi E, Addis A, Batzu L, Mariotto S, Ferrari S, Conti M, et al. Late presentation of NMOSD as rapidly progressive leukoencephalopathy with atypical clinical and radiological findings. Mult Scler. 2018;24(5):685–8. Scholar
  64. 64.
    Ogawa R, Nakashima I, Takahashi T, Kaneko K, Akaishi T, Takai Y, et al. MOG antibody-positive, benign, unilateral, cerebral cortical encephalitis with epilepsy. Neurol Neuroimmunol Neuroinflamm. 2017;4(2):e322. Scholar
  65. 65.•
    Escudero D, Guasp M, Arino H, Gaig C, Martinez-Hernandez E, Dalmau J, et al. Antibody-associated CNS syndromes without signs of inflammation in the elderly. Neurology. 2017;89(14):1471–5. This study highlights the importance of recognizing characteristic clinical syndromes associted with CNS autoimmunity as paraclinical findings suggestive of inflammation may be lacking, especially in the elderly.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Sechi G, Sechi E, Fois C, Kumar N. Advances in clinical determinants and neurological manifestations of B vitamin deficiency in adults. Nutr Rev. 2016;74(5):281–300. Scholar
  67. 67.
    Sechi E, Addis A, Fadda G, Minafra L, Bravata V, Sechi G. Teaching NeuroImages: subacute encephalopathy in a young woman with THTR2 gene mutation. Neurology. 2015;85(14):e108–9. Scholar
  68. 68.
    Lopez-Chiriboga AS, Yoon JW, Siegel JL, Harriott AM, Pirris S, Eidelman BH, et al. Granulomatous angiitis of the central nervous system associated with Hodgkin's lymphoma: case report and literature review. J Stroke Cerebrovasc Dis. 2018;27(1):e5–8. Scholar
  69. 69.
    Auriel E, Charidimou A, Gurol ME, Ni J, Van Etten ES, Martinez-Ramirez S, et al. Validation of clinicoradiological criteria for the diagnosis of cerebral amyloid angiopathy-related inflammation. JAMA Neurol. 2016;73(2):197–202. Scholar
  70. 70.
    Flanagan EP, Chowdhary VR, McCarthy JT, Smyrk TC, Chari ST, Kumar N. IgG4-related (neurologic) disease: diagnostic challenges, clinical clues and expanding spectrum. Int J Rheum Dis. 2015;18(7):807–9. Scholar
  71. 71.
    Probasco JC, Solnes L, Nalluri A, Cohen J, Jones KM, Zan E, et al. Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm. 2017;4(4):e352. Scholar
  72. 72.
    Rey C, Koric L, Guedj E, Felician O, Kaphan E, Boucraut J, et al. Striatal hypermetabolism in limbic encephalitis. J Neurol. 2012;259(6):1106–10. Scholar
  73. 73.
    Jesse S, Brettschneider J, Sussmuth SD, Landwehrmeyer BG, von Arnim CA, Ludolph AC, et al. Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases. J Neurol. 2011;258(6):1034–41. Scholar
  74. 74.
    Janssen JC, Godbolt AK, Ioannidis P, Thompson EJ, Rossor MN. The prevalence of oligoclonal bands in the CSF of patients with primary neurodegenerative dementia. J Neurol. 2004;251(2):184–8. Scholar
  75. 75.
    Maddalena A, Papassotiropoulos A, Muller-Tillmanns B, Jung HH, Hegi T, Nitsch RM, et al. Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to beta-amyloid peptide42. Arch Neurol. 2003;60(9):1202–6. Scholar
  76. 76.
    McGuire LI, Peden AH, Orru CD, Wilham JM, Appleford NE, Mallinson G, et al. Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease. Ann Neurol. 2012;72(2):278–85. Scholar
  77. 77.
    Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J, Friedman D. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology. 2012;79(11):1094–100. Scholar
  78. 78.
    Baykan B, Gungor Tuncer O, Vanli-Yavuz EN, Baysal Kirac L, Gundogdu G, Bebek N, et al. Delta brush pattern is not unique to NMDAR encephalitis: evaluation of two independent long-term EEG cohorts. Clin EEG Neurosci. 2018;49(4):278–84. Scholar
  79. 79.
    Horta ES, Lennon VA, Lachance DH, Jenkins SM, Smith CY, McKeon A, et al. Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res. 2014;20(14):3862–9. Scholar
  80. 80.
    Hoftberger R, Sabater L, Marignier R, Aboul-Enein F, Bernard-Valnet R, Rauschka H, et al. An optimized immunohistochemistry technique improves NMO-IgG detection: study comparison with cell-based assays. PLoS One. 2013;8(11):e79083. Scholar
  81. 81.
    Titulaer MJ, Hoftberger R, Iizuka T, Leypoldt F, McCracken L, Cellucci T, et al. Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2014;75(3):411–28. Scholar
  82. 82.
    Lang K, Pruss H. Frequencies of neuronal autoantibodies in healthy controls: estimation of disease specificity. Neurol Neuroimmunol Neuroinflamm. 2017;4(5):e386. Scholar
  83. 83.
    Jarius S, Paul F, Aktas O, Asgari N, Dale RC, de Seze J, et al. MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation. 2018;15(1):134. Scholar
  84. 84.
    McCracken L, Zhang J, Greene M, Crivaro A, Gonzalez J, Kamoun M, et al. Improving the antibody-based evaluation of autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm. 2017;4(6):e404. Scholar
  85. 85.
    van Sonderen A, Roelen DL, Stoop JA, Verdijk RM, Haasnoot GW, Thijs RD, et al. Anti-LGI1 encephalitis is strongly associated with HLA-DR7 and HLA-DRB4. Ann Neurol. 2017;81(2):193–8. Scholar
  86. 86.
    McKeon A, Apiwattanakul M, Lachance DH, Lennon VA, Mandrekar JN, Boeve BF, et al. Positron emission tomography-computed tomography in paraneoplastic neurologic disorders: systematic analysis and review. Arch Neurol. 2010;67(3):322–9. Scholar
  87. 87.
    Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004;56(5):715–9. Scholar
  88. 88.
    Toledano M, Britton JW, McKeon A, Shin C, Lennon VA, Quek AM, et al. Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology. 2014;82(18):1578–86. Scholar
  89. 89.
    Sechi E, Morris PP, McKeon A, Pittock SJ, Hinson SR, Weinshenker BG, et al. Glial fibrillary acidic protein IgG related myelitis: characterisation and comparison with aquaporin-4-IgG myelitis. J Neurol Neurosurg Psychiatry. 2018.
  90. 90.
    Iizuka T, Sakai F, Ide T, Monzen T, Yoshii S, Iigaya M, et al. Anti-NMDA receptor encephalitis in Japan: long-term outcome without tumor removal. Neurology. 2008;70(7):504–11. Scholar
  91. 91.
    Szots M, Marton A, Kover F, Kiss T, Berki T, Nagy F, et al. Natural course of LGI1 encephalitis: 3-5 years of follow-up without immunotherapy. J Neurol Sci. 2014;343(1–2):198–202. Scholar
  92. 92.
    Finke C, Kopp UA, Pruss H, Dalmau J, Wandinger KP, Ploner CJ. Cognitive deficits following anti-NMDA receptor encephalitis. J Neurol Neurosurg Psychiatry. 2012;83(2):195–8. Scholar
  93. 93.
    Finke C, Pruss H, Heine J, Reuter S, Kopp UA, Wegner F, et al. Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. JAMA Neurol. 2017;74(1):50–9. Scholar
  94. 94.
    McKeon GL, Robinson GA, Ryan AE, Blum S, Gillis D, Finke C, et al. Cognitive outcomes following anti-N-methyl-D-aspartate receptor encephalitis: a systematic review. J Clin Exp Neuropsychol. 2018;40(3):234–52. Scholar
  95. 95.
    McKeon GL, Scott JG, Spooner DM, Ryan AE, Blum S, Gillis D, et al. Cognitive and social functioning deficits after anti-N-methyl-D-aspartate receptor encephalitis: an exploratory case series. J Int Neuropsychol Soc. 2016;22(8):828–38. Scholar
  96. 96.
    de Bruijn M, Aarsen FK, van Oosterhout MP, van der Knoop MM, Catsman-Berrevoets CE, Schreurs MWJ, et al. Long-term neuropsychological outcome following pediatric anti-NMDAR encephalitis. Neurology. 2018;90(22):e1997–2005. Scholar
  97. 97.
    Dubey D, Kothapalli N, McKeon A, Flanagan EP, Lennon VA, Klein CJ, et al. Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction. J Neuroimmunol. 2018;323:62–72. Scholar
  98. 98.
    Evangelopoulos ME, Andreadou E, Koutsis G, Koutoulidis V, Anagnostouli M, Katsika P, et al. Treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders with rituximab using a maintenance treatment regimen and close CD19 B cell monitoring. A six-year follow-up. J Neurol Sci. 2017;372:92–6. Scholar
  99. 99.
    Lee WJ, Lee ST, Byun JI, Sunwoo JS, Kim TJ, Lim JA, et al. Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort. Neurology. 2016;86(18):1683–91. Scholar
  100. 100.
    Lee WJ, Lee ST, Moon J, Sunwoo JS, Byun JI, Lim JA, et al. Tocilizumab in autoimmune encephalitis refractory to rituximab: an institutional cohort study. Neurotherapeutics. 2016;13(4):824–32. Scholar
  101. 101.
    Lim JA, Lee ST, Moon J, Jun JS, Park BS, Byun JI, et al. New feasible treatment for refractory autoimmune encephalitis: low-dose interleukin-2. J Neuroimmunol. 2016;299:107–11. Scholar
  102. 102.
    Scheibe F, Pruss H, Mengel AM, Kohler S, Numann A, Kohnlein M, et al. Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology. 2017;88(4):366–70. Scholar
  103. 103.
    Flanagan EP, Aksamit AJ, Kumar N, Morparia NP, Keegan BM, Weinshenker BG. Simultaneous PML-IRIS and myelitis in a patient with neuromyelitis optica spectrum disorder. Neurol Clin Pract. 2013;3(5):448–51. Scholar
  104. 104.
    Sharma R, Chakraborty T, Buadi FK, Beam E, Pureza VS, Pagani-Estevez GL, et al. Clinical reasoning: a 56-year-old woman with acute vertigo and diplopia. Neurology. 2018;90(16):748–52. Scholar
  105. 105.••
    Armangue T, Spatola M, Vlagea A, Mattozzi S, Carceles-Cordon M, Martinez-Heras E, et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol. 2018;17(9):760–72. This study reports for the first time a disproportionally high occurrence of autoimmune encephalitis following HSV encephalitis with important therapeutical implications.CrossRefPubMedGoogle Scholar
  106. 106.
    Kao JC, Liao B, Markovic SN, Klein CJ, Naddaf E, Staff NP, et al. Neurological complications associated with anti-programmed death 1 (PD-1) antibodies. JAMA Neurol. 2017;74(10):1216–22. Scholar
  107. 107.
    Larkin J, Chmielowski B, Lao CD, Hodi FS, Sharfman W, Weber J, et al. Neurologic serious adverse events associated with nivolumab plus ipilimumab or nivolumab alone in advanced melanoma, including a case series of encephalitis. Oncologist. 2017;22(6):709–18. Scholar
  108. 108.
    Cohen DA, Lopez-Chiriboga AS, Pittock SJ, Gadoth A, Zekeridou A, Boilson BA, et al. Posttransplant autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm. 2018;5(6):e497. Scholar
  109. 109.
    Rathore GS, Leung KS, Muscal E. Autoimmune encephalitis following bone marrow transplantation. Pediatr Neurol. 2015;53(3):253–6. Scholar
  110. 110.
    Zhao CZ, Erickson J, Dalmau J. Clinical reasoning: agitation and psychosis in a patient after renal transplantation. Neurology. 2012;79(5):e41–4. Scholar
  111. 111.
    Seeley WW, Marty FM, Holmes TM, Upchurch K, Soiffer RJ, Antin JH, et al. Post-transplant acute limbic encephalitis: clinical features and relationship to HHV6. Neurology. 2007;69(2):156–65. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurologyMayo ClinicRochesterUSA
  2. 2.Department Laboratory Medicine and PathologyMayo ClinicRochesterUSA

Personalised recommendations