UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Paraneoplastic and autoimmune encephalitis

Authors
Josep Dalmau, MD, PhD
Myrna R Rosenfeld, MD, PhD
Section Editor
Lisa M DeAngelis, MD, FAAN, FANA
Deputy Editor
April F Eichler, MD, MPH

INTRODUCTION

Encephalitis is an inflammatory condition of the brain with many etiologies. There are several types of encephalitis that are immune-mediated, including the classic paraneoplastic encephalitis syndromes and the encephalitis syndromes associated with antibodies against neuronal cell surface/synaptic proteins. The latter are often referred to as autoimmune encephalitis.

While the paraneoplastic encephalitis syndromes are invariably cancer-related, the autoimmune encephalitis syndromes may occur in the presence or absence of cancer. Thus, nomenclature can be confusing, as the paraneoplastic encephalitis syndromes are autoimmune, and autoimmune encephalitis may be paraneoplastic. In this topic, the term autoimmune encephalitis refers specifically to those syndromes that are associated with antibodies to neuronal cell surface/synaptic proteins.  

An overview of paraneoplastic syndromes and other paraneoplastic disorders are discussed separately. (See "Overview of paraneoplastic syndromes of the nervous system" and "Paraneoplastic syndromes affecting peripheral nerve and muscle" and "Paraneoplastic syndromes affecting the spinal cord and dorsal root ganglia" and "Paraneoplastic cerebellar degeneration" and "Opsoclonus myoclonus syndrome".)

PARANEOPLASTIC ENCEPHALITIS

Clinical features — Paraneoplastic encephalitis may manifest as limbic or brainstem encephalitis or be part of widespread involvement of the neuraxis, as in paraneoplastic encephalomyelitis. In the majority of cases, symptoms have an acute to subacute onset, and evaluation of the cerebrospinal fluid (CSF) often shows abnormalities such as pleocytosis, increased protein concentration, oligoclonal bands, and elevated immunoglobulin G (IgG) index, suggesting an inflammatory process. In more than half of patients, the neurologic syndrome develops before the cancer diagnosis is known.

Limbic encephalitis — Limbic encephalitis refers to an inflammatory process localized to structures of the limbic system (eg, hippocampus, amygdala, hypothalamus, cingulate gyrus, limbic cortex), although the pathologic, clinical and radiological findings are often not confined to these areas. Limbic encephalitis is considered a classical paraneoplastic syndrome, defined as a disorder that is commonly due to a paraneoplastic process. However, as noted below, limbic encephalitis is the main manifestation of several of the autoimmune encephalitis syndromes that may occur without a cancer association. (See 'Autoimmune encephalitis' below.)    

                                

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jul 2017. | This topic last updated: Jul 26, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000; 123 ( Pt 7):1481.
  2. Lawn ND, Westmoreland BF, Kiely MJ, et al. Clinical, magnetic resonance imaging, and electroencephalographic findings in paraneoplastic limbic encephalitis. Mayo Clin Proc 2003; 78:1363.
  3. Basu S, Alavi A. Role of FDG-PET in the clinical management of paraneoplastic neurological syndrome: detection of the underlying malignancy and the brain PET-MRI correlates. Mol Imaging Biol 2008; 10:131.
  4. Alamowitch S, Graus F, Uchuya M, et al. Limbic encephalitis and small cell lung cancer. Clinical and immunological features. Brain 1997; 120 ( Pt 6):923.
  5. Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu--associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore) 1992; 71:59.
  6. Henson RA, Hoffman HL, Urich H. Encephalomyelitis with carcinoma. Brain 1965; 88:449.
  7. Moragas M, Martínez-Yélamos S, Majós C, et al. Rhombencephalitis: a series of 97 patients. Medicine (Baltimore) 2011; 90:256.
  8. Pillay N, Gilbert JJ, Ebers GC, Brown JD. Internuclear ophthalmoplegia and "optic neuritis": paraneoplastic effects of bronchial carcinoma. Neurology 1984; 34:788.
  9. Saiz A, Bruna J, Stourac P, et al. Anti-Hu-associated brainstem encephalitis. J Neurol Neurosurg Psychiatry 2009; 80:404.
  10. Voltz R, Gultekin SH, Rosenfeld MR, et al. A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. N Engl J Med 1999; 340:1788.
  11. Jean WC, Dalmau J, Ho A, Posner JB. Analysis of the IgG subclass distribution and inflammatory infiltrates in patients with anti-Hu-associated paraneoplastic encephalomyelitis. Neurology 1994; 44:140.
  12. Dalmau J, Graus F, Villarejo A, et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004; 127:1831.
  13. Graus F, Keime-Guibert F, Reñe R, et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 2001; 124:1138.
  14. Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology 1998; 50:652.
  15. Dalmau J, Furneaux HM, Cordon-Cardo C, Posner JB. The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues. Am J Pathol 1992; 141:881.
  16. Sillevis Smitt P, Grefkens J, de Leeuw B, et al. Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. J Neurol 2002; 249:745.
  17. Mut M, Schiff D, Dalmau J. Paraneoplastic recurrent multifocal encephalitis presenting with epilepsia partialis continua. J Neurooncol 2005; 72:63.
  18. Shavit YB, Graus F, Probst A, et al. Epilepsia partialis continua: a new manifestation of anti-Hu-associated paraneoplastic encephalomyelitis. Ann Neurol 1999; 45:255.
  19. Kinirons P, O'Dwyer JP, Connolly S, Hutchinson M. Paraneoplastic limbic encephalitis presenting as lingual epilepsia partialis continua. J Neurol 2006; 253:256.
  20. Jacobs DA, Fung KM, Cook NM, et al. Complex partial status epilepticus associated with anti-Hu paraneoplastic syndrome. J Neurol Sci 2003; 213:77.
  21. Honnorat J, Didelot A, Karantoni E, et al. Autoimmune limbic encephalopathy and anti-Hu antibodies in children without cancer. Neurology 2013; 80:2226.
  22. van Broekhoven F, de Graaf MT, Bromberg JE, et al. Human chorionic gonadotropin treatment of anti-Hu-associated paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2010; 81:1341.
  23. Shams'ili S, de Beukelaar J, Gratama JW, et al. An uncontrolled trial of rituximab for antibody associated paraneoplastic neurological syndromes. J Neurol 2006; 253:16.
  24. Darnell RB, DeAngelis LM. Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies. Lancet 1993; 341:21.
  25. Byrne T, Mason WP, Posner JB, Dalmau J. Spontaneous neurological improvement in anti-Hu associated encephalomyelitis. J Neurol Neurosurg Psychiatry 1997; 62:276.
  26. Dalmau J, Gultekin SH, Voltz R, et al. Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders. Brain 1999; 122 ( Pt 1):27.
  27. Waragai M, Chiba A, Uchibori A, et al. Anti-Ma2 associated paraneoplastic neurological syndrome presenting as encephalitis and progressive muscular atrophy. J Neurol Neurosurg Psychiatry 2006; 77:111.
  28. Mathew RM, Vandenberghe R, Garcia-Merino A, et al. Orchiectomy for suspected microscopic tumor in patients with anti-Ma2-associated encephalitis. Neurology 2007; 68:900.
  29. Hoffmann LA, Jarius S, Pellkofer HL, et al. Anti-Ma and anti-Ta associated paraneoplastic neurological syndromes: 22 newly diagnosed patients and review of previous cases. J Neurol Neurosurg Psychiatry 2008; 79:767.
  30. Al-Thubaiti I, Al-Hayek K, Binfalah M. Anti-Ma-associated encephalitis due to dysgerminoma in a woman with Swyer syndrome. Neurology 2013; 80:1439.
  31. Blumenthal DT, Salzman KL, Digre KB, et al. Early pathologic findings and long-term improvement in anti-Ma2-associated encephalitis. Neurology 2006; 67:146.
  32. Yu Z, Kryzer TJ, Griesmann GE, et al. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001; 49:146.
  33. Vernino S, Tuite P, Adler CH, et al. Paraneoplastic chorea associated with CRMP-5 neuronal antibody and lung carcinoma. Ann Neurol 2002; 51:625.
  34. Muehlschlegel S, Okun MS, Foote KD, et al. Paraneoplastic chorea with leukoencephalopathy presenting with obsessive-compulsive and behavioral disorder. Mov Disord 2005; 20:1523.
  35. Werry C, Götz F, Wurster U, et al. Paraneoplastic autoimmune encephalitis associated with CV2/CRMP-5 IgG antineuronal antibodies in a patient with thymoma. J Neurol 2009; 256:129.
  36. Rickman OB, Parisi JE, Yu Z, et al. Fulminant autoimmune cortical encephalitis associated with thymoma treated with plasma exchange. Mayo Clin Proc 2000; 75:1321.
  37. De Camilli P, Thomas A, Cofiell R, et al. The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer. J Exp Med 1993; 178:2219.
  38. Murinson BB, Guarnaccia JB. Stiff-person syndrome with amphiphysin antibodies: distinctive features of a rare disease. Neurology 2008; 71:1955.
  39. Martinez-Hernandez E, Ariño H, McKeon A, et al. Clinical and Immunologic Investigations in Patients With Stiff-Person Spectrum Disorder. JAMA Neurol 2016; 73:714.
  40. Ariño H, Höftberger R, Gresa-Arribas N, et al. Paraneoplastic Neurological Syndromes and Glutamic Acid Decarboxylase Antibodies. JAMA Neurol 2015; 72:874.
  41. Tüzün E, Rossi JE, Karner SF, et al. Adenylate kinase 5 autoimmunity in treatment refractory limbic encephalitis. J Neuroimmunol 2007; 186:177.
  42. Sutton IJ, Barnett MH, Watson JD, et al. Paraneoplastic brainstem encephalitis and anti-Ri antibodies. J Neurol 2002; 249:1597.
  43. Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011; 77:179.
  44. Zuliani L, Graus F, Giometto B, et al. Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition. J Neurol Neurosurg Psychiatry 2012; 83:638.
  45. Vitaliani R, Mason W, Ances B, et al. Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Ann Neurol 2005; 58:594.
  46. Dalmau J, Tüzün E, Wu HY, et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61:25.
  47. Shimazaki H, Ando Y, Nakano I, Dalmau J. Reversible limbic encephalitis with antibodies against the membranes of neurones of the hippocampus. J Neurol Neurosurg Psychiatry 2007; 78:324.
  48. Iizuka T, Sakai F, Ide T, et al. Anti-NMDA receptor encephalitis in Japan: long-term outcome without tumor removal. Neurology 2008; 70:504.
  49. Seki M, Suzuki S, Iizuka T, et al. Neurological response to early removal of ovarian teratoma in anti-NMDAR encephalitis. J Neurol Neurosurg Psychiatry 2008; 79:324.
  50. Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7:1091.
  51. Florance-Ryan N, Dalmau J. Update on anti-N-methyl-D-aspartate receptor encephalitis in children and adolescents. Curr Opin Pediatr 2010; 22:739.
  52. Dalmau J, Lancaster E, Martinez-Hernandez E, et al. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011; 10:63.
  53. Wingfield T, McHugh C, Vas A, et al. Autoimmune encephalitis: a case series and comprehensive review of the literature. QJM 2011; 104:921.
  54. Hacohen Y, Wright S, Waters P, et al. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 2013; 84:748.
  55. Kayser MS, Titulaer MJ, Gresa-Arribas N, Dalmau J. Frequency and characteristics of isolated psychiatric episodes in anti–N-methyl-d-aspartate receptor encephalitis. JAMA Neurol 2013; 70:1133.
  56. Smith JH, Dhamija R, Moseley BD, et al. N-methyl-D-aspartate receptor autoimmune encephalitis presenting with opsoclonus-myoclonus: treatment response to plasmapheresis. Arch Neurol 2011; 68:1069.
  57. Kurian M, Lalive PH, Dalmau JO, Horvath J. Opsoclonus-myoclonus syndrome in anti-N-methyl-D-aspartate receptor encephalitis. Arch Neurol 2010; 67:118.
  58. Fitzpatrick AS, Gray OM, McConville J, McDonnell GV. Opsoclonus-myoclonus syndrome associated with benign ovarian teratoma. Neurology 2008; 70:1292.
  59. Kawachi I, Saji E, Toyoshima Y, et al. Treatment responsive opsoclonus-ataxia associated with ovarian teratoma. J Neurol Neurosurg Psychiatry 2010; 81:581.
  60. Armangue T, Titulaer MJ, Sabater L, et al. A novel treatment-responsive encephalitis with frequent opsoclonus and teratoma. Ann Neurol 2014; 75:435.
  61. Florance NR, Davis RL, Lam C, et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66:11.
  62. Luca N, Daengsuwan T, Dalmau J, et al. Anti-N-methyl-D-aspartate receptor encephalitis: a newly recognized inflammatory brain disease in children. Arthritis Rheum 2011; 63:2516.
  63. Armangue T, Petit-Pedrol M, Dalmau J. Autoimmune encephalitis in children. J Child Neurol 2012; 27:1460.
  64. 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; 12:157.
  65. Baizabal-Carvallo JF, Stocco A, Muscal E, Jankovic J. The spectrum of movement disorders in children with anti-NMDA receptor encephalitis. Mov Disord 2013; 28:543.
  66. Armangue T, Titulaer MJ, Málaga I, et al. Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 2013; 162:850.
  67. Raha S, Gadgil P, Sankhla C, Udani V. Nonparaneoplastic anti-N-methyl-D-aspartate receptor encephalitis: a case series of four children. Pediatr Neurol 2012; 46:246.
  68. Gable M, Glaser C. Anti-N-Methyl-d-Aspartate Receptor Encephalitis Appearing as a New-Onset Psychosis: Disease Course in Children and Adolescents Within the California Encephalitis Project. Pediatr Neurol 2017; 72:25.
  69. Wright S, Hacohen Y, Jacobson L, et al. N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children. Arch Dis Child 2015; 100:521.
  70. Titulaer MJ, McCracken L, Gabilondo I, et al. Late-onset anti-NMDA receptor encephalitis. Neurology 2013; 81:1058.
  71. Schmitt SE, Pargeon K, Frechette ES, et al. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 2012; 79:1094.
  72. Leypoldt F, Buchert R, Kleiter I, et al. Fluorodeoxyglucose positron emission tomography in anti-N-methyl-D-aspartate receptor encephalitis: distinct pattern of disease. J Neurol Neurosurg Psychiatry 2012; 83:681.
  73. Prüss H, Dalmau J, Harms L, et al. Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin. Neurology 2010; 75:1735.
  74. Gresa-Arribas N, Titulaer MJ, Torrents A, et al. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol 2014; 13:167.
  75. Dahm L, Ott C, Steiner J, et al. Seroprevalence of autoantibodies against brain antigens in health and disease. Ann Neurol 2014; 76:82.
  76. Martinez-Hernandez E, Horvath J, Shiloh-Malawsky Y, et al. Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis. Neurology 2011; 77:589.
  77. Okamoto S, Hirano T, Takahashi Y, et al. Paraneoplastic limbic encephalitis caused by ovarian teratoma with autoantibodies to glutamate receptor. Intern Med 2007; 46:1019.
  78. Sansing LH, Tüzün E, Ko MW, et al. A patient with encephalitis associated with NMDA receptor antibodies. Nat Clin Pract Neurol 2007; 3:291.
  79. Gable MS, Gavali S, Radner A, et al. Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis. Eur J Clin Microbiol Infect Dis 2009; 28:1421.
  80. Dale RC, Irani SR, Brilot F, et al. N-methyl-D-aspartate receptor antibodies in pediatric dyskinetic encephalitis lethargica. Ann Neurol 2009; 66:704.
  81. Vincent A, Bien CG, Irani SR, Waters P. Autoantibodies associated with diseases of the CNS: new developments and future challenges. Lancet Neurol 2011; 10:759.
  82. Zandi MS, Irani SR, Follows G, et al. Limbic encephalitis associated with antibodies to the NMDA receptor in Hodgkin lymphoma. Neurology 2009; 73:2039.
  83. Sanmaneechai O, Song JL, Nevadunsky N, et al. Anti-N-methyl-d-aspartate encephalitis with ovarian cystadenofibroma. Pediatr Neurol 2013; 48:232.
  84. Lebas A, Husson B, Didelot A, et al. Expanding spectrum of encephalitis with NMDA receptor antibodies in young children. J Child Neurol 2010; 25:742.
  85. Williams TJ, Benavides DR, Patrice KA, et al. Association of Autoimmune Encephalitis With Combined Immune Checkpoint Inhibitor Treatment for Metastatic Cancer. JAMA Neurol 2016; 73:928.
  86. Leypoldt F, Titulaer MJ, Aguilar E, et al. Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis: case report. Neurology 2013; 81:1637.
  87. Armangue T, Moris G, Cantarín-Extremera V, et al. Autoimmune post-herpes simplex encephalitis of adults and teenagers. Neurology 2015; 85:1736.
  88. Armangue T, Leypoldt F, Málaga I, et al. Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol 2014; 75:317.
  89. Prüss H, Finke C, Höltje M, et al. N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 2012; 72:902.
  90. Mohammad SS, Sinclair K, Pillai S, et al. Herpes simplex encephalitis relapse with chorea is associated with autoantibodies to N-Methyl-D-aspartate receptor or dopamine-2 receptor. Mov Disord 2014; 29:117.
  91. Hacohen Y, Deiva K, Pettingill P, et al. N-methyl-D-aspartate receptor antibodies in post-herpes simplex virus encephalitis neurological relapse. Mov Disord 2014; 29:90.
  92. Sutcu M, Akturk H, Somer A, et al. Role of Autoantibodies to N-Methyl-d-Aspartate (NMDA) Receptor in Relapsing Herpes Simplex Encephalitis: A Retrospective, One-Center Experience. J Child Neurol 2016; 31:345.
  93. Titulaer MJ, Leypoldt F, Dalmau J. Antibodies to N-methyl-D-aspartate and other synaptic receptors in choreoathetosis and relapsing symptoms post-herpes virus encephalitis. Mov Disord 2014; 29:3.
  94. Suppiej A, Nosadini M, Zuliani L, et al. Plasma exchange in pediatric anti-NMDAR encephalitis: A systematic review. Brain Dev 2016; 38:613.
  95. Dale RC, Brilot F, Duffy LV, et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 2014; 83:142.
  96. Viaccoz A, Desestret V, Ducray F, et al. Clinical specificities of adult male patients with NMDA receptor antibodies encephalitis. Neurology 2014; 82:556.
  97. Nosadini M, Mohammad SS, Ramanathan S, et al. Immune therapy in autoimmune encephalitis: a systematic review. Expert Rev Neurother 2015; 15:1391.
  98. Finke C, Kopp UA, Prüss H, et al. Cognitive deficits following anti-NMDA receptor encephalitis. J Neurol Neurosurg Psychiatry 2012; 83:195.
  99. Gabilondo I, Saiz A, Galán L, et al. Analysis of relapses in anti-NMDAR encephalitis. Neurology 2011; 77:996.
  100. 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; 9:776.
  101. Fukata Y, Lovero KL, Iwanaga T, et al. Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. Proc Natl Acad Sci U S A 2010; 107:3799.
  102. Andrade DM, Tai P, Dalmau J, Wennberg R. Tonic seizures: a diagnostic clue of anti-LGI1 encephalitis? Neurology 2011; 76:1355.
  103. Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011; 69:892.
  104. Klein CJ, Lennon VA, Aston PA, et al. Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping. JAMA Neurol 2013; 70:229.
  105. Sen A, Wang J, Laue-Gizzi H, et al. Pathognomonic seizures in limbic encephalitis associated with anti-LGI1 antibodies. Lancet 2014; 383:2018.
  106. Navarro V, Kas A, Apartis E, et al. Motor cortex and hippocampus are the two main cortical targets in LGI1-antibody encephalitis. Brain 2016; 139:1079.
  107. 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; 133:2734.
  108. Ariño H, Armangué T, Petit-Pedrol M, et al. Anti-LGI1-associated cognitive impairment: Presentation and long-term outcome. Neurology 2016; 87:759.
  109. Jacob S, Irani SR, Rajabally YA, et al. Hypothermia in VGKC antibody-associated limbic encephalitis. J Neurol Neurosurg Psychiatry 2008; 79:202.
  110. Vincent A, Buckley C, Schott JM, et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 2004; 127:701.
  111. Wong SH, Saunders MD, Larner AJ, et al. An effective immunotherapy regimen for VGKC antibody-positive limbic encephalitis. J Neurol Neurosurg Psychiatry 2010; 81:1167.
  112. Irani SR, Gelfand JM, Bettcher BM, et al. Effect of rituximab in patients with leucine-rich, glioma-inactivated 1 antibody-associated encephalopathy. JAMA Neurol 2014; 71:896.
  113. van Sonderen A, Thijs RD, Coenders EC, et al. Anti-LGI1 encephalitis: Clinical syndrome and long-term follow-up. Neurology 2016; 87:1449.
  114. Finke C, Prüss H, Heine J, et al. Evaluation of Cognitive Deficits and Structural Hippocampal Damage in Encephalitis With Leucine-Rich, Glioma-Inactivated 1 Antibodies. JAMA Neurol 2017; 74:50.
  115. Lai M, Hughes EG, Peng X, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009; 65:424.
  116. Bataller L, Galiano R, García-Escrig M, et al. Reversible paraneoplastic limbic encephalitis associated with antibodies to the AMPA receptor. Neurology 2010; 74:265.
  117. Graus F, Boronat A, Xifró X, et al. The expanding clinical profile of anti-AMPA receptor encephalitis. Neurology 2010; 74:857.
  118. Höftberger R, van Sonderen A, Leypoldt F, et al. Encephalitis and AMPA receptor antibodies: Novel findings in a case series of 22 patients. Neurology 2015; 84:2403.
  119. Joubert B, Kerschen P, Zekeridou A, et al. Clinical Spectrum of Encephalitis Associated With Antibodies Against the α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor: Case Series and Review of the Literature. JAMA Neurol 2015; 72:1163.
  120. 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; 13:276.
  121. Spatola M, Petit-Pedrol M, Simabukuro MM, et al. Investigations in GABAA receptor antibody-associated encephalitis. Neurology 2017; 88:1012.
  122. Spatola M, Petit-Pedrol M, Rosenfeld M, et al. Novel findings in anti-GABAa receptor encephalitis. Neurology 2016; 86:3.
  123. Höftberger R, Titulaer MJ, Sabater L, et al. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology 2013; 81:1500.
  124. Boronat A, Sabater L, Saiz A, et al. GABA(B) receptor antibodies in limbic encephalitis and anti-GAD-associated neurologic disorders. Neurology 2011; 76:795.
  125. Kruer MC, Hoeftberger R, Lim KY, et al. Aggressive course in encephalitis with opsoclonus, ataxia, chorea, and seizures: the first pediatric case of γ-aminobutyric acid type B receptor autoimmunity. JAMA Neurol 2014; 71:620.
  126. 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; 9:67.
  127. Lancaster E, Huijbers MG, Bar V, et al. Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia. Ann Neurol 2011; 69:303.
  128. Irani SR, Pettingill P, Kleopa KA, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 2012; 72:241.
  129. Joubert B, Saint-Martin M, Noraz N, et al. 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 2016; 73:1115.
  130. van Sonderen A, Ariño H, Petit-Pedrol M, et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology 2016; 87:521.
  131. Sabater L, Gaig C, Gelpi E, et al. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol 2014; 13:575.
  132. Högl B, Heidbreder A, Santamaria J, et al. IgLON5 autoimmunity and abnormal behaviours during sleep. Lancet 2015; 385:1590.
  133. Simabukuro MM, Sabater L, Adoni T, et al. Sleep disorder, chorea, and dementia associated with IgLON5 antibodies. Neurol Neuroimmunol Neuroinflamm 2015; 2:e136.
  134. Gaig C, Graus F, Compta Y, et al. Clinical manifestations of the anti-IgLON5 disease. Neurology 2017; 88:1736.
  135. Gelpi E, Höftberger R, Graus F, et al. Neuropathological criteria of anti-IgLON5-related tauopathy. Acta Neuropathol 2016; 132:531.
  136. 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; 73:120.
  137. Balint B, Jarius S, Nagel S, et al. Progressive encephalomyelitis with rigidity and myoclonus: a new variant with DPPX antibodies. Neurology 2014; 82:1521.
  138. Tobin WO, Lennon VA, Komorowski L, et al. DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology 2014; 83:1797.
  139. Mas N, Saiz A, Leite MI, et al. Antiglycine-receptor encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry 2011; 82:1399.
  140. Hutchinson M, Waters P, McHugh J, et al. Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology 2008; 71:1291.
  141. Clerinx K, Breban T, Schrooten M, et al. Progressive encephalomyelitis with rigidity and myoclonus: resolution after thymectomy. Neurology 2011; 76:303.
  142. Turner MR, Irani SR, Leite MI, et al. Progressive encephalomyelitis with rigidity and myoclonus: glycine and NMDA receptor antibodies. Neurology 2011; 77:439.
  143. Carvajal-González A, Leite MI, Waters P, et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain 2014; 137:2178.
  144. Martinez-Hernandez E, Sepulveda M, Rostásy K, et al. Antibodies to aquaporin 4, myelin-oligodendrocyte glycoprotein, and the glycine receptor α1 subunit in patients with isolated optic neuritis. JAMA Neurol 2015; 72:187.
  145. Prüss H, Rothkirch M, Kopp U, et al. Limbic encephalitis with mGluR5 antibodies and immunotherapy-responsive prosopagnosia. Neurology 2014; 83:1384.
  146. Lancaster E, Martinez-Hernandez E, Titulaer MJ, et al. Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology 2011; 77:1698.
  147. Mat A, Adler H, Merwick A, et al. Ophelia syndrome with metabotropic glutamate receptor 5 antibodies in CSF. Neurology 2013; 80:1349.
  148. Gresa-Arribas N, Planagumà J, Petit-Pedrol M, et al. Human neurexin-3α antibodies associate with encephalitis and alter synapse development. Neurology 2016; 86:2235.
  149. Fang B, McKeon A, Hinson SR, et al. Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Novel Meningoencephalomyelitis. JAMA Neurol 2016; 73:1297.
  150. Flanagan EP, Hinson SR, Lennon VA, et al. Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients. Ann Neurol 2017; 81:298.
  151. Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol 2008; 7:327.
  152. Blanc F, Ben Abdelghani K, Schramm F, et al. Whipple limbic encephalitis. Arch Neurol 2011; 68:1471.
  153. Blondin NA, Vortmeyer AO, Harel NY. Paraneoplastic syndrome of inappropriate antidiuretic hormone mimicking limbic encephalitis. Arch Neurol 2011; 68:1591.
  154. Lejuste F, Thomas L, Picard G, et al. Neuroleptic intolerance in patients with anti-NMDAR encephalitis. Neurol Neuroimmunol Neuroinflamm 2016; 3:e280.
  155. Jarius S, Hoffmann L, Clover L, et al. CSF findings in patients with voltage gated potassium channel antibody associated limbic encephalitis. J Neurol Sci 2008; 268:74.
  156. Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004; 75:1135.
  157. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15:391.
  158. Darnell RB, Posner JB. A new cause of limbic encephalopathy. Brain 2005; 128:1745.
  159. Vedeler CA, Antoine JC, Giometto B, et al. Management of paraneoplastic neurological syndromes: report of an EFNS Task Force. Eur J Neurol 2006; 13:682.
  160. Vernino S, O'Neill BP, Marks RS, et al. Immunomodulatory treatment trial for paraneoplastic neurological disorders. Neuro Oncol 2004; 6:55.
  161. Keime-Guibert F, Graus F, Broët P, et al. Clinical outcome of patients with anti-Hu-associated encephalomyelitis after treatment of the tumor. Neurology 1999; 53:1719.