An Overview of Autoimmune and Paraneoplastic Encephalitides

Abstract

The understanding of the manifestations, mechanisms, and management of autoimmune encephalitis has expanded dramatically in recent decades. Immune-mediated encephalitides are comparable in incidence and prevalence to infectious etiologies, and are associated with significant morbidity, especially when there is a delay in recognition and treatment. As such, clinicians from many specialties must develop a functional understanding of these disorders. Herein we provide an overview of the autoimmune and paraneoplastic encephalitides, including those associated with either intracellular or cell surface/synaptic neuronal autoantibodies. After briefly reviewing the current understanding of the pathobiology of autoimmune encephalitis, we combine a neuroanatomical approach with specific antibody syndromes to provide the reader with a clinically relevant review of these disorders. The clinical manifestations, diagnosis, and management of autoimmune encephalitis are reviewed, with an emphasis on clinical relevance. We also introduce updates in the field, including autoimmune encephalitis associated with novel cancer immunotherapies, infectious triggers of autoimmune encephalitis, and autoimmune encephalitis with demyelinating overlap syndromes.

Keywords

autoimmune - paraneoplastic - encephalitis - antibodies - immunotherapy

• References

• 1 McKeon A, Pittock SJ. Paraneoplastic encephalomyelopathies: pathology and mechanisms. Acta Neuropathol 2011; 122 (04) 381-400
• 2 Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol 2008; 7 (04) 327-340
• 3 Albert ML, Darnell JC, Bender A, Francisco LM, Bhardwaj N, Darnell RB. Tumor-specific killer cells in paraneoplastic cerebellar degeneration. Nat Med 1998; 4 (11) 1321-1324
• 4 Greenlee JE, Clawson SA, Hill KE. , et al. Anti-Yo antibody uptake and interaction with its intracellular target antigen causes Purkinje cell death in rat cerebellar slice cultures: a possible mechanism for paraneoplastic cerebellar degeneration in humans with gynecological or breast cancers. PLoS One 2015; 10 (04) e0123446
• 5 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 (02) 298-309
• 6 Fang B, McKeon A, Hinson SR. , et al. Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol 2016; 73 (11) 1297-1307
• 7 Lancaster E, Dalmau J. Neuronal autoantigens--pathogenesis, associated disorders and antibody testing. Nat Rev Neurol 2012; 8 (07) 380-390
• 8 Gleichman AJ, Spruce LA, Dalmau J, Seeholzer SH, Lynch DR. Anti-NMDA receptor encephalitis antibody binding is dependent on amino acid identity of a small region within the GluN1 amino terminal domain. J Neurosci 2012; 32 (32) 11082-11094
• 9 Mikasova L, De Rossi P, Bouchet D. , et al. Disrupted surface cross-talk between NMDA and Ephrin-B2 receptors in anti-NMDA encephalitis. Brain 2012; 135 (Pt 5): 1606-1621
• 10 Planagumà J, Leypoldt F, Mannara F. , et al. Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice. Brain 2015; 138 (Pt 1): 94-109
• 11 Graus F, Titulaer MJ, Balu R. , et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15 (04) 391-404
• 12 Wilson MR, Naccache SN, Samayoa E. , et al. Actionable diagnosis of neuroleptospirosis by next-generation sequencing. N Engl J Med 2014; 370 (25) 2408-2417
• 13 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 (02) 157-165
• 14 Linnoila JJ, Rosenfeld MR, Dalmau J. Neuronal surface antibody-mediated autoimmune encephalitis. Semin Neurol 2014; 34 (04) 458-466
• 15 Dubey D, Pittock SJ, Kelly CR. , et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 2018; 83 (01) 166-177
• 16 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 (07) 899-904
• 17 Toledano M, Pittock SJ. Autoimmune epilepsy. Semin Neurol 2015; 35 (03) 245-258
• 18 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) 1094-1100
• 19 van Sonderen A, Thijs RD, Coenders EC. , et al. Anti-LGI1 encephalitis: Clinical syndrome and long-term follow-up. Neurology 2016; 87 (14) 1449-1456
• 20 Steriade C, Mirsattari SM, Murray BJ, Wennberg R. Subclinical temporal EEG seizure pattern in LGI1-antibody-mediated encephalitis. Epilepsia 2016; 57 (08) e155-e160
• 21 Aurangzeb S, Symmonds M, Knight RK, Kennett R, Wehner T, Irani SR. LGI1-antibody encephalitis is characterised by frequent, multifocal clinical and subclinical seizures. Seizure 2017; 50: 14-17
• 22 Probasco JC, Solnes L, Nalluri A. , et al. Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm 2017; 4 (04) e352
• 23 Scheid R, Lincke T, Voltz R, von Cramon DY, Sabri O. Serial 18F-fluoro-2-deoxy-D-glucose positron emission tomography and magnetic resonance imaging of paraneoplastic limbic encephalitis. Arch Neurol 2004; 61 (11) 1785-1789
• 24 Ances BM, Vitaliani R, Taylor RA. , et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain 2005; 128 (Pt 8): 1764-1777
• 25 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 (07) 681-686
• 26 Linnoila J, Pittock SJ. Autoantibody-associated central nervous system neurologic disorders. Semin Neurol 2016; 36 (04) 382-396
• 27 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 (02) 167-177
• 28 Majed M, Fryer JP, McKeon A, Lennon VA, Pittock SJ. Clinical utility of testing AQP4-IgG in CSF: guidance for physicians. Neurol Neuroimmunol Neuroinflamm 2016; 3 (03) e231
• 29 Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med 2003; 349 (16) 1543-1554
• 30 McKeon A, Apiwattanakul M, Lachance DH. , et al. Positron emission tomography-computed tomography in paraneoplastic neurologic disorders: systematic analysis and review. Arch Neurol 2010; 67 (03) 322-329
• 31 Gorman MP. Update on diagnosis, treatment, and prognosis in opsoclonus-myoclonus-ataxia syndrome. Curr Opin Pediatr 2010; 22 (06) 745-750
• 32 Titulaer MJ, Soffietti R, Dalmau J. , et al; European Federation of Neurological Societies. Screening for tumours in paraneoplastic syndromes: report of an EFNS task force. Eur J Neurol 2011; 18 (01) 19-e3
• 33 Dalmau J, Tüzün E, Wu HY. , et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61 (01) 25-36
• 34 Heine J, Prüss H, Bartsch T, Ploner CJ, Paul F, Finke C. Imaging of autoimmune encephalitis--Relevance for clinical practice and hippocampal function. Neuroscience 2015; 309: 68-83
• 35 Leypoldt F, Armangue T, Dalmau J. Autoimmune encephalopathies. Ann N Y Acad Sci 2015; 1338: 94-114
• 36 Florance NR, Davis RL, Lam C. , et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66 (01) 11-18
• 37 Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000; 123 (Pt 7): 1481-1494
• 38 Tüzün E, Dalmau J. Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist 2007; 13 (05) 261-271
• 39 Lawn ND, Westmoreland BF, Kiely MJ, Lennon VA, Vernino S. Clinical, magnetic resonance imaging, and electroencephalographic findings in paraneoplastic limbic encephalitis. Mayo Clin Proc 2003; 78 (11) 1363-1368
• 40 Bastiaansen AEM, van Sonderen A, Titulaer MJ. Autoimmune encephalitis with anti-leucine-rich glioma-inactivated 1 or anti-contactin-associated protein-like 2 antibodies (formerly called voltage-gated potassium channel-complex antibodies). Curr Opin Neurol 2017; 30 (03) 302-309
• 41 Flanagan EP, Kotsenas AL, Britton JW. , et al. Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures. Neurol Neuroimmunol Neuroinflamm 2015; 2 (06) e161
• 42 Kim HJ, Paul F, Lana-Peixoto MA. , et al; Guthy-Jackson Charitable Foundation NMO International Clinical Consortium & Biorepository. MRI characteristics of neuromyelitis optica spectrum disorder: an international update. Neurology 2015; 84 (11) 1165-1173
• 43 Graus F, Keime-Guibert F, Reñe R. , et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 2001; 124 (Pt 6): 1138-1148
• 44 Lee KS, Higgins MJ, Patel BM, Larson JS, Rady MY. Paraneoplastic coma and acquired central alveolar hypoventilation as a manifestation of brainstem encephalitis in a patient with ANNA-1 antibody and small-cell lung cancer. Neurocrit Care 2006; 4 (02) 137-139
• 45 Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology 1998; 50 (03) 652-657
• 46 Saiz A, Bruna J, Stourac P. , et al. Anti-Hu-associated brainstem encephalitis. J Neurol Neurosurg Psychiatry 2009; 80 (04) 404-407
• 47 Pittock SJ, Lucchinetti CF, Lennon VA. Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol 2003; 53 (05) 580-587
• 48 Dalmau J, Graus F, Villarejo A. , et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004; 127 (Pt 8): 1831-1844
• 49 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 (23) 1788-1795
• 50 Ortega Suero G, Sola-Valls N, Escudero D, Saiz A, Graus F. Anti-Ma and anti-Ma2-associated paraneoplastic neurological syndromes. Neurologia 2018; 33 (01) 18-27
• 51 Shahrizaila N, Yuki N. Bickerstaff brainstem encephalitis and Fisher syndrome: anti-GQ1b antibody syndrome. J Neurol Neurosurg Psychiatry 2013; 84 (05) 576-583
• 52 Fisher M. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med 1956; 255 (02) 57-65
• 53 Chiba A, Kusunoki S, Shimizu T, Kanazawa I. Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome. Ann Neurol 1992; 31 (06) 677-679
• 54 Yuki N, Sato S, Tsuji S, Hozumi I, Miyatake T. An immunologic abnormality common to Bickerstaff's brain stem encephalitis and Fisher's syndrome. J Neurol Sci 1993; 118 (01) 83-87
• 55 Yuki N. Fisher syndrome and Bickerstaff brainstem encephalitis (Fisher-Bickerstaff syndrome). J Neuroimmunol 2009; 215 (1-2): 1-9
• 56 Koga M, Kusunoki S, Kaida K. , et al. Nationwide survey of patients in Japan with Bickerstaff brainstem encephalitis: epidemiological and clinical characteristics. J Neurol Neurosurg Psychiatry 2012; 83 (12) 1210-1215
• 57 Chida K, Nomura H, Konno H, Takase S, Itoyama Y. Recurrent Miller Fisher syndrome: clinical and laboratory features and HLA antigens. J Neurol Sci 1999; 165 (02) 139-143
• 58 Hamaguchi T, Yamaguchi K, Komai K. , et al. Recurrent anti-GQ1b IgG antibody syndrome showing different phenotypes in different periods. J Neurol Neurosurg Psychiatry 2003; 74 (09) 1350
• 59 Orr CF, Storey CE. Recurrent Miller-Fisher syndrome. J Clin Neurosci 2004; 11 (03) 307-309
• 60 Jones AL, Flanagan EP, Pittock SJ. , et al. Responses to and outcomes of treatment of autoimmune cerebellar ataxia in adults. JAMA Neurol 2015; 72 (11) 1304-1312
• 61 McKeon A, Tracy JA, Pittock SJ, Parisi JE, Klein CJ, Lennon VA. Purkinje cell cytoplasmic autoantibody type 1 accompaniments: the cerebellum and beyond. Arch Neurol 2011; 68 (10) 1282-1289
• 62 Russo C, Cohn SL, Petruzzi MJ, de Alarcon PA. Long-term neurologic outcome in children with opsoclonus-myoclonus associated with neuroblastoma: a report from the Pediatric Oncology Group. Med Pediatr Oncol 1997; 28 (04) 284-288
• 63 Klaas JP, Ahlskog JE, Pittock SJ. , et al. Adult-onset opsoclonus-myoclonus syndrome. Arch Neurol 2012; 69 (12) 1598-1607
• 64 Toledano M, Britton JW, McKeon A. , et al. Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology 2014; 82 (18) 1578-1586
• 65 Yshii LM, Hohlfeld R, Liblau RS. Inflammatory CNS disease caused by immune checkpoint inhibitors: status and perspectives. Nat Rev Neurol 2017; 13 (12) 755-763
• 66 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 (08) 928-933
• 67 Schneider S, Potthast S, Komminoth P, Schwegler G, Böhm S. PD-1 checkpoint inhibitor associated autoimmune encephalitis. Case Rep Oncol 2017; 10 (02) 473-478
• 68 Larkin J, Chmielowski B, Lao CD. , 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 (06) 709-718
• 69 Touat M, Talmasov D, Ricard D, Psimaras D. Neurological toxicities associated with immune-checkpoint inhibitors. Curr Opin Neurol 2017; 30 (06) 659-668
• 70 Papadopoulos KP, Romero RS, Gonzalez G, Dix JE, Lowy I, Fury M. Anti-Hu-associated autoimmune limbic encephalitis in a patient with PD-1 inhibitor-responsive myxoid chondrosarcoma. Oncologist 2018; 23 (01) 118-120
• 71 Gust J, Hay KA, Hanafi LA. , et al. Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discov 2017; 7 (12) 1404-1419
• 72 Titulaer MJ, Höftberger R, Iizuka T. , et al. Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2014; 75 (03) 411-428
• 73 Wingerchuk DM, Banwell B, Bennett JL. , et al; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015; 85 (02) 177-189
• 74 Sellner J, Boggild M, Clanet M. , et al. EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol 2010; 17 (08) 1019-1032
• 75 Baheerathan A, Brownlee WJ, Chard DT, Shields K, Gregory R, Trip SA. Antecedent anti-NMDA receptor encephalitis in two patients with multiple sclerosis. Mult Scler Relat Disord 2017; 12: 20-22
• 76 Uzawa A, Mori M, Takahashi Y, Ogawa Y, Uchiyama T, Kuwabara S. Anti-N-methyl D-aspartate-type glutamate receptor antibody-positive limbic encephalitis in a patient with multiple sclerosis. Clin Neurol Neurosurg 2012; 114 (04) 402-404
• 77 Fleischmann R, Prüss H, Rosche B. , et al. Severe cognitive impairment associated with intrathecal antibodies to the NR1 subunit of the N-methyl-D-aspartate receptor in a patient with multiple sclerosis. JAMA Neurol 2015; 72 (01) 96-99
• 78 Ramberger M, Bsteh G, Schanda K. , et al. NMDA receptor antibodies: a rare association in inflammatory demyelinating diseases. Neurol Neuroimmunol Neuroinflamm 2015; 2 (05) e141
• 79 Planagumà J, Haselmann H, Mannara F. , et al. Ephrin-B2 prevents N-methyl-D-aspartate receptor antibody effects on memory and neuroplasticity. Ann Neurol 2016; 80 (03) 388-400
• 80 Bradshaw MJ, Venkatesan A. Herpes simplex virus-1 encephalitis in adults: pathophysiology, diagnosis, and management. Neurotherapeutics 2016; 13 (03) 493-508
• 81 Schäbitz WR, Rogalewski A, Hagemeister C, Bien CG. VZV brainstem encephalitis triggers NMDA receptor immunoreaction. Neurology 2014; 83 (24) 2309-2311
• 82 Armangue T, Leypoldt F, Málaga I. , et al. Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol 2014; 75 (02) 317-323
• 83 Armangue T, Moris G, Cantarín-Extremera V. , et al; Spanish Prospective Multicentric Study of Autoimmunity in Herpes Simplex Encephalitis. Autoimmune post-herpes simplex encephalitis of adults and teenagers. Neurology 2015; 85 (20) 1736-1743
• 84 Linnoila JJ, Binnicker MJ, Majed M, Klein CJ, McKeon A. CSF herpes virus and autoantibody profiles in the evaluation of encephalitis. Neurol Neuroimmunol Neuroinflamm 2016; 3 (04) e245
• 85 Bradshaw MJ, Pawate S, Lennon VA, Bloch KC, Brown KM. Herpes simplex virus 1 encephalitis associated with voltage-gated calcium channel autoimmunity. Neurology 2015; 85 (24) 2176-2177
• 86 Shillito P, Molenaar PC, Vincent A. , et al. Acquired neuromyotonia: evidence for autoantibodies directed against K+ channels of peripheral nerves. Ann Neurol 1995; 38 (05) 714-722
• 87 Sinha S, Newsom-Davis J, Mills K, Byrne N, Lang B, Vincent A. Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome). Lancet 1991; 338 (8759): 75-77
• 88 Barber PA, Anderson NE, Vincent A. Morvan's syndrome associated with voltage-gated K+ channel antibodies. Neurology 2000; 54 (03) 771-772
• 89 Buckley C, Oger J, Clover L. , et al. Potassium channel antibodies in two patients with reversible limbic encephalitis. Ann Neurol 2001; 50 (01) 73-78
• 90 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 (08) 776-785
• 91 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 (09) 2734-2748
• 92 van Sonderen A, Petit-Pedrol M, Dalmau J, Titulaer MJ. The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis. Nat Rev Neurol 2017; 13 (05) 290-301
• 93 Graus F, Vincent A, Pozo-Rosich P. , et al. Anti-glial nuclear antibody: marker of lung cancer-related paraneoplastic neurological syndromes. J Neuroimmunol 2005; 165 (1-2): 166-171
• 94 Pittock SJ, Lucchinetti CF, Parisi JE. , et al. Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol 2005; 58 (01) 96-107
• 95 Chan KH, Vernino S, Lennon VA. ANNA-3 anti-neuronal nuclear antibody: marker of lung cancer-related autoimmunity. Ann Neurol 2001; 50 (03) 301-311
• 96 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 (02) 146-154
• 97 Pittock SJ, Yoshikawa H, Ahlskog JE. , et al. Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction. Mayo Clin Proc 2006; 81 (09) 1207-1214
• 98 Ariño H, Höftberger R, Gresa-Arribas N. , et al. Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol 2015; 72 (08) 874-881
• 99 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): 27-39
• 100 Greenlee JE, Brashear HR. Antibodies to cerebellar Purkinje cells in patients with paraneoplastic cerebellar degeneration and ovarian carcinoma. Ann Neurol 1983; 14 (06) 609-613
• 101 Vernino S, Lennon VA. New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol 2000; 47 (03) 297-305
• 102 McKeon A, Lennon VA, LaChance DH, Klein CJ, Pittock SJ. Striational antibodies in a paraneoplastic context. Muscle Nerve 2013; 47 (04) 585-587
• 103 Bataller L, Wade DF, Graus F, Stacey HD, Rosenfeld MR, Dalmau J. Antibodies to Zic4 in paraneoplastic neurologic disorders and small-cell lung cancer. Neurology 2004; 62 (05) 778-782
• 104 Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 1976; 26 (11) 1054-1059
• 105 McKeon A, Lennon VA, Lachance DH, Fealey RD, Pittock SJ. Ganglionic acetylcholine receptor autoantibody: oncological, neurological, and serological accompaniments. Arch Neurol 2009; 66 (06) 735-741
• 106 Lai M, Hughes EG, Peng X. , et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009; 65 (04) 424-434
• 107 Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005; 202 (04) 473-477
• 108 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 (01) 120-128
• 109 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 (03) 276-286
• 110 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 (01) 67-76
• 111 Hutchinson M, Waters P, McHugh J. , et al. Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology 2008; 71 (16) 1291-1292
• 112 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 (06) 575-586
• 113 Honorat JA, Komorowski L, Josephs KA. , et al. IgLON5 antibody: Neurological accompaniments and outcomes in 20 patients. Neurol Neuroimmunol Neuroinflamm 2017; 4 (05) e385
• 114 Marignier R, Chenevier F, Rogemond V. , et al. Metabotropic glutamate receptor type 1 autoantibody-associated cerebellitis: a primary autoimmune disease?. Arch Neurol 2010; 67 (05) 627-630
• 115 Lopez-Chiriboga AS, Komorowski L, Kümpfel T. , et al. Metabotropic glutamate receptor type 1 autoimmunity: clinical features and treatment outcomes. Neurology 2016; 86 (11) 1009-1013
• 116 Lancaster E, Martinez-Hernandez E, Titulaer MJ. , et al. Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology 2011; 77 (18) 1698-1701
• 117 Reindl M, Di Pauli F, Rostásy K, Berger T. The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 2013; 9 (08) 455-461
• 118 Gresa-Arribas N, Planagumà J, Petit-Pedrol M. , et al. Human neurexin-3α antibodies associate with encephalitis and alter synapse development. Neurology 2016; 86 (24) 2235-2242
• 119 Bernal F, Shams'ili S, Rojas I. , et al. Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin's disease. Neurology 2003; 60 (02) 230-234
• 120 Zalewski NL, Lennon VA, Lachance DH, Klein CJ, Pittock SJ, Mckeon A. P/Q- and N-type calcium-channel antibodies: Oncological, neurological, and serological accompaniments. Muscle Nerve 2016; 54 (02) 220-227