Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cb9f654ff-5kfdg Total loading time: 0 Render date: 2025-08-09T05:40:23.654Z Has data issue: false hasContentIssue false

Chapter 7 - Autoimmunity Against Proteins Associated with Voltage-Gated Potassium Channels

from Section 3 - Specific Syndromes and Diseases

Published online by Cambridge University Press:  27 January 2022

Josep Dalmau  and
Francesc Graus
Josep Dalmau
Affiliation:
Universitat de Barcelona
Francesc Graus
Affiliation:
Universitat de Barcelona
Get access

Summary

The description of VGKC antibodies detected by radioimmunoassay (RIA) led to mischaracterizing as autoimmune an extensive number of syndromes in many patients who in fact did not have autoimmune disorders. We now know that VGKC antibodies demonstrated by RIA have no clinical value, unless the presence of LGI1 and CASPR2 antibodies are demonstrated by cell-based assays. Limbic encephalitis is by far the most frequent disorder associated with LGI1 antibodies. It usually occurs in the elderly (median age ~65 years) and ~65% are male. Anti-LGI1 encephalitis is frequently preceded by faciobrachial dystonic seizures that are very characteristic of this disorder and should prompt early-onset immunotherapy to prevent the development of memory and cognitive deficits. Most patients do not have cancer or other types of tumours, with the exception of thymoma in a few cases. Patients with CASPR2 antibodies may present with symptoms of encephalitis or peripheral nervous system hyperexcitability (neuromyotonia), and sometimes they develop Morvan syndrome. This disorder is characterized by a severe sleep dysfunction named agrypnia excitata, along with hallucinations, cognitive decline, dysautonomia, and neuromyotonia. Up to 50% of patients with Morvan syndrome have an underlying thymoma. As with other encephalitis associated with antibodies against neuronal surface antigens, patients with encephalitis associated with LGI1 and CASPR2 antibodies usually respond to immunotherapy.

Keywords

Autoimmune encephalitislimbic encephalitisLGI1 antibodiesCASPR2 antibodiesMorvan syndromevoltage-gated potassium channels (VGKC antibodies)agrypnia excitata

Information

Type
Chapter
Information
Autoimmune Encephalitis and Related Disorders of the Nervous System , pp. 191 - 209
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Vincent, A, Roberts, M, Willison, H, Lang, B, Newsom-Davis, J. Autoantibodies, neurotoxins and the nervous system. J Physiol Paris 1995;89:129–136.CrossRefGoogle ScholarPubMed
Motomura, M, Johnston, I, Lang, B, Vincent, A, Newsom-Davis, J. An improved diagnostic assay for Lambert–Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 1995;58:85–87.Google Scholar
Vincent, A, Newsom Davis, J. Anti-acetylcholine receptor antibodies. J Neurol Neurosurg Psychiatry 1980;43:590–600.Google Scholar
Shillito, P, Molenaar, PC, Vincent, A, et al. Acquired neuromyotonia: evidence for autoantibodies directed against K+ channels of peripheral nerves. Ann Neurol 1995;38:714–722.Google Scholar
Graus, F, Saiz, A, Dalmau, J. Antibodies and neuronal autoimmune disorders of the CNS. J Neurol 2009;257:509–517Google Scholar
Graus, F, Delattre, JY, Antoine, JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004;75:1135–1140.Google Scholar
Ances, BM, Vitaliani, R, Taylor, RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain 2005;128:1764–1777.Google Scholar
Dalmau, JG, Christian, G, Graus, F. Autoantibodies to synaptic receptors and neuronal cell surface proteins in autoimmune diseases of the central nervous system. Physiol Rev 2017;97:839–887.Google Scholar
Jarius, S, Wildemann, B. ‘Medusa head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26 and anti-VGCC. J Neuroinflammation 2015;12:167.Google Scholar
Jarius, S, Wildemann, B. ‘Medusa head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook. J Neuroinflammation 2015;12:168.Google Scholar
Jarius, S, Wildemann, B. ‘Medusa-head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 1: anti-mGluR1, anti-Homer-3, anti-Sj/ITPR1 and anti-CARP VIII. J Neuroinflammation 2015;12:166.Google Scholar
Newsom-Davis, J, Mills, KR. Immunological associations of acquired neuromyotonia (Isaac’s syndrome): report of five cases and literature review. Brain 1993;116:453–469.Google Scholar
Sinha, S, Newsom-Davis, J, Mills, K, et al. Autoimmune aetiology for acquired neuromyotonia (Isaacs’ syndrome). Lancet 1991;338:75–77.Google Scholar
Newsom-Davis, J, Buckley, C, Clover, L, et al. Autoimmune disorders of neuronal potassium channels. Ann N Y Acad Sci 2003;998:202–210.Google Scholar
Hart, IK, Maddison, P, Newsom-Davis, J, Vincent, A, Mills, KR. Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain 2002;125:1887–1895.Google Scholar
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;124:2417–2426.Google Scholar
Irani, SR, Pettingill, P, Kleopa, KA, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 2012;72:241–255.Google Scholar
Buckley, C, Oger, J, Clover, L, et al. Potassium channel antibodies in two patients with reversible limbic encephalitis. Ann Neurol 2001;50:73–78.Google Scholar
Vincent, A, Buckley, C, Schott, JM, et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 2004;127:701–712.CrossRefGoogle ScholarPubMed
Thieben, MJ, Lennon, VA, Boeve, BF, et al. Potentially reversible autoimmune limbic encephalitis with neuronal potassium channel antibody. Neurology 2004;62:1177–1182.Google Scholar
McKnight, K, Jiang, Y, Hart, Y, et al. Serum antibodies in epilepsy and seizure-associated disorders. Neurology 2005;65:1730–1736.Google Scholar
Majoie, HJ, de Baets, M, Renier, W, Lang, B, Vincent, A. Antibodies to voltage-gated potassium and calcium channels in epilepsy. Epilepsy Res 2006;71:135–141.Google Scholar
Tan, KM, Lennon, VA, Klein, CJ, Boeve, BF, Pittock, SJ. Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology 2008;70:1883–1890.Google Scholar
Dhamija, R, Renaud, DL, Pittock, SJ, et al. Neuronal voltage-gated potassium channel complex autoimmunity in children. Pediatr Neurol 2011;44:275–281.Google Scholar
Vincent, A, Buckley, C, Lang, B, Irani, S. Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology 2009;72:99.Google Scholar
Klein, CJ, Lennon, VA, Aston, PA, McKeon, A, Pittock, SJ. Chronic pain as a manifestation of potassium channel-complex autoimmunity. Neurology 2012;79:1136–1144.Google Scholar
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;9:776–785.Google Scholar
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;133:2734–2748.Google Scholar
Rosenfeld, MR, Titulaer, MJ, Dalmau, J. Paraneoplastic syndromes and autoimmune encephalitis, five new things. Neurol Clin Pract 2012;1:215–222.Google Scholar
Lang, B, Makuch, M, Moloney, T, et al. Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies. J Neurol Neurosurg Psychiatry 2017;88:353–361.Google Scholar
Paterson, RW, Zandi, MS, Armstrong, R, Vincent, A, Schott, JM. Clinical relevance of positive voltage-gated potassium channel (VGKC)-complex antibodies: experience from a tertiary referral centre. J Neurol Neurosurg Psychiatry 2014;85:625–630.Google Scholar
Hacohen, Y, Singh, R, Rossi, M, et al. Clinical relevance of voltage-gated potassium channel-complex antibodies in children. Neurology 2015;85:967–975.Google Scholar
van Sonderen, A, Schreurs, MW, de Bruijn, MA, et al. The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. Neurology 2016;86:1692–1699.Google Scholar
Graus, F, Gorman, MP. Voltage-gated potassium channel antibodies: game over. Neurology 2016;86:1657–1658.Google Scholar
Graus, F, Titulaer, MJ, Balu, R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.Google Scholar
Gadoth, A, Pittock, SJ, Dubey, D, et al. Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients. Ann Neurol 2017;82:79–92.CrossRefGoogle ScholarPubMed
Dubey, D, Alqallaf, A, Hays, R, et al. Neurological autoantibody prevalence in epilepsy of unknown etiology. JAMA Neurol 2017;74:397–402.CrossRefGoogle ScholarPubMed
Elisak, M, Krysl, D, Hanzalova, J, et al. The prevalence of neural antibodies in temporal lobe epilepsy and the clinical characteristics of seropositive patients. Seizure 2018;63:1–6.CrossRefGoogle ScholarPubMed
Brenner, T, Sills, GJ, Hart, Y, et al. Prevalence of neurologic autoantibodies in cohorts of patients with new and established epilepsy. Epilepsia 2013;54:1028–1035.Google Scholar
Vincent, A, Pettingill, P, Pettingill, R, et al. Association of leucine-rich glioma inactivated protein 1, contactin-associated protein 2, and contactin 2 antibodies with clinical features and patient-reported pain in acquired neuromyotonia. JAMA Neurol 2018;75:1519–1527.Google Scholar
Klein, CJ, Lennon, VA, Aston, PA, et al. Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping. JAMA Neurol 2013;70:229–234.Google Scholar
Binks, SNM, Klein, CJ, Waters, P, Pittock, SJ, Irani, SR. LGI1, CASPR2 and related antibodies: a molecular evolution of the phenotypes. J Neurol Neurosurg Psychiatry 2018;89:526–534.Google Scholar
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;33:18161–18174.Google Scholar
Petit-Pedrol, M, Sell, J, Planaguma, J, et al. LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain 2018;141:3144–3159.Google Scholar
van Sonderen, A, Thijs, RD, Coenders, EC, et al. Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology 2016;87:1449–1456.Google Scholar
Celicanin, M, Blaabjerg, M, Maersk-Moller, C, et al. Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies: a national cohort study. Eur J Neurol 2017;24:999–1005.Google Scholar
Binks, S, Varley, J, Lee, W, et al. Distinct HLA associations of LGI1 and CASPR2-antibody diseases. Brain 2018;141:2263–2271.Google Scholar
van Sonderen, A, Roelen, DL, Stoop, JA, et al. Anti-LGI1 encephalitis is strongly associated with HLA-DR7 and HLA-DRB4. Ann Neurol 2017;81:193–198.Google Scholar
Kim, TJ, Lee, ST, Moon, J, et al. Anti-LGI1 encephalitis is associated with unique HLA subtypes. Ann Neurol 2017;81:183–192.Google Scholar
Mueller, SH, Farber, A, Pruss, H, et al. Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis. Ann Neurol 2018;83:863–869.Google Scholar
Bien, CG, Vincent, A, Barnett, MH, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain 2012;135:1622–1638.Google Scholar
Arino, H, Armangue, T, Petit-Pedrol, M, et al. Anti-LGI1-associated cognitive impairment: presentation and long-term outcome. Neurology 2016;87:759–765.Google Scholar
Park, DC, Murman, DL, Perry, KD, Bruch, LA. An autopsy case of limbic encephalitis with voltage-gated potassium channel antibodies. Eur J Neurol 2007;14:e5–6.Google Scholar
Dunstan, EJ, Winer, JB. Autoimmune limbic encephalitis causing fits, rapidly progressive confusion and hyponatraemia. Age Ageing 2006;35:536–537.Google Scholar
Khan, NL, Jeffree, MA, Good, C, Macleod, W, Al-Sarraj, S. Histopathology of VGKC antibody-associated limbic encephalitis. Neurology 2009;72:1703–1705.Google Scholar
Schultze-Amberger, J, Pehl, D, Stenzel, W. LGI-1-positive limbic encephalitis: a clinicopathological study. J Neurol 2012;259:2478–2480.Google Scholar
Körtvelyessy, P, Bauer, J, Stoppel, CM, et al. Complement-associated neuronal loss in a patient with CASPR2 antibody-associated encephalitis. Neurol Neuroimmunol Neuroinflamm 2015;2:e75.Google Scholar
Sundal, C, Vedeler, C, Miletic, H, Andersen, O. Morvan syndrome with Caspr2 antibodies: clinical and autopsy report. J Neurol Sci 2017;372:453–455.Google Scholar
Maat, P, de Beukelaar, JW, Jansen, C, et al. Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease. Neurol Neuroimmunol Neuroinflamm 2015;2:e178.Google Scholar
Thompson, J, Bi, M, Murchison, AG, et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain 2018;141:348–356.Google Scholar
Irani, SR, Michell, AW, Lang, B, et al. Faciobrachial dystonic seizures precede LGI1 antibody limbic encephalitis. Ann Neurol 2011;69:892–900.Google Scholar
Navarro, V, Kas, A, Apartis, E, et al. Motor cortex and hippocampus are the two main cortical targets in LGI1-antibody encephalitis. Brain 2016;139:1079–1093.Google Scholar
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;136:3151–3162.Google Scholar
Rachdi, A, Dupouy, J, Benaiteau, M, et al. Leucine-rich glioma-inactivated 1 encephalitis: broadening the sphere. Tremor Other Hyperkinet Mov (N Y) 2019;9.Google Scholar
Loddenkemper, T, Kellinghaus, C, Gandjour, J, et al. Localising and lateralising value of ictal piloerection. J Neurol Neurosurg Psychiatry 2004;75:879–883.Google Scholar
Rocamora, R, Becerra, JL, Fossas, P, et al. Pilomotor seizures: an autonomic semiology of limbic encephalitis? Seizure 2014;23:670–673.Google Scholar
Wieser, S, Kelemen, A, Barsi, P, et al. Pilomotor seizures and status in non-paraneoplastic limbic encephalitis. Epileptic Disord 2005;7:205–211.Google Scholar
Naasan, G, Irani, SR, Bettcher, BM, Geschwind, MD, Gelfand, JM. Episodic bradycardia as neurocardiac prodrome to voltage-gated potassium channel complex/leucine-rich, glioma inactivated 1 antibody encephalitis. JAMA Neurol 2014;71:1300–1304.Google Scholar
Nilsson, AC, Blaabjerg, M. More evidence of a neurocardiac prodrome in anti-LGI1 encephalitis. J Neurol Sci 2015;357:310–311.Google Scholar
Britton, JW, Ghearing, GR, Benarroch, EE, Cascino, GD. The ictal bradycardia syndrome: localization and lateralization. Epilepsia 2006;47:737–744.Google Scholar
Tofaris, GK, Irani, SR, Cheeran, BJ, et al. Immunotherapy-responsive chorea as the presenting feature of LGI1-antibody encephalitis. Neurology 2012;79:195–196.Google Scholar
Ramdhani, RA, Frucht, SJ. Isolated chorea associated with LGI1 antibody. Tremor Other Hyperkinet Mov (N Y) 2014;4.Google Scholar
Iranzo, A, Graus, F, Clover, L, et al. Rapid eye movement sleep behavior disorder and potassium channel antibody-associated limbic encephalitis. Ann Neurol 2006;59:178–181.Google Scholar
Cornelius, JR, Pittock, SJ, McKeon, A, et al. Sleep manifestations of voltage-gated potassium channel complex autoimmunity. Arch Neurol 2011;68:733–738.Google Scholar
Butler, CR, Miller, TD, Kaur, MS, et al. Persistent anterograde amnesia following limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex. J Neurol Neurosurg Psychiatry 2014;85:387–391.Google Scholar
Finke, C, Pruss, 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;74:50–59.Google Scholar
Bettcher, BM, Gelfand, JM, Irani, SR, et al. More than memory impairment in voltage-gated potassium channel complex encephalopathy. Eur J Neurol 2014;21:1301–1310.Google Scholar
Jang, Y, Lee, ST, Lim, JA, et al. Psychiatric symptoms delay the diagnosis of anti-LGI1 encephalitis. J Neuroimmunol 2018;317:8–14.Google Scholar
Balint, B, Vincent, A, Meinck, HM, Irani, SR, Bhatia, KP. Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. Brain 2018;141:13–36.Google Scholar
Geschwind, MD, Tan, KM, Lennon, VA, et al. Voltage-gated potassium channel autoimmunity mimicking Creutzfeldt-Jakob disease. Arch Neurol 2008;65:1341–1346.Google Scholar
McQuillan, RF, Bargman, JM. Hyponatraemia caused by LGI1-associated limbic encephalitis. NDT plus 2011;4:424–426.Google ScholarPubMed
Head, K, Gong, S, Joseph, S, et al. Defining the expression pattern of the LGI1 gene in BAC transgenic mice. Mammalian Genome 2007;18:328–337.Google Scholar
Gadoth, A, Zekeridou, A, Klein, CJ, et al. Elevated LGI1-IgG CSF index predicts worse neurological outcome. Ann Clin Transl Neurol 2018;5:646–650.Google Scholar
Escudero, D, Guasp, M, Arino, H, et al. Antibody-associated CNS syndromes without signs of inflammation in the elderly. Neurology 2017;89:1471–1475.CrossRefGoogle Scholar
Flanagan, EP, Kotsenas, AL, Britton, JW, et al. Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures. Neurol Neuroimmunol Neuroinflamm 2015;2:e161.Google Scholar
Grativvol, RS, Simabukuro, MM, Spera, RR, et al. Imaging findings in faciobrachial dystonic seizures associated with LGI-1 antibodies. Arq Neuropsiquiatr 2016;74:947.Google Scholar
Lopez Chiriboga, AS, Siegel, JL, Tatum, WO, Shih, JJ, Flanagan, EP. Striking basal ganglia imaging abnormalities in LGI1 ab faciobrachial dystonic seizures. Neurol Neuroimmunol Neuroinflamm 2017;4:e336.Google Scholar
Heine, J, Pruss, H, Bartsch, T, et al. Imaging of autoimmune encephalitis: relevance for clinical practice and hippocampal function. Neuroscience 2015;309:68–83.Google Scholar
Moloney, P, Boylan, R, Elamin, M, et al. Semi-quantitative analysis of cerebral FDG-PET reveals striatal hypermetabolism and normal cortical metabolism in a case of VGKCC limbic encephalitis. Neuroradiol J 2017;30:160–163.Google Scholar
Rey, C, Koric, L, Guedj, E, et al. Striatal hypermetabolism in limbic encephalitis. J Neurol 2012;259:1106–1110.Google Scholar
Maeder-Ingvar, M, Prior, JO, Irani, SR, et al. FDG-PET hyperactivity in basal ganglia correlating with clinical course in anti-NDMA-R antibodies encephalitis. J Neurol Neurosurg Psychiatry 2011;82:235–236.Google Scholar
Morbelli, S, Arbizu, J, Booij, J, et al. The need of standardization and of large clinical studies in an emerging indication of [(18)F]FDG PET: the autoimmune encephalitis. Eur J Nucl Med Molec Imag 2017;44:353–357.CrossRefGoogle Scholar
Fauser, S, Talazko, J, Wagner, K, et al. FDG-PET and MRI in potassium channel antibody-associated non-paraneoplastic limbic encephalitis: correlation with clinical course and neuropsychology. Acta Neurol Scand 2005;111:338–343.Google Scholar
Ances, BM, Vitaliani, R, Taylor, RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain 2005;128:1764–1777.Google Scholar
Kamaleshwaran, KK, Iyer, RS, Antony, J, Radhakrishnan, EK, Shinto, A. 18F-FDG PET/CT findings in voltage-gated potassium channel limbic encephalitis. Clin Nucl Med 2013;38:392–394.Google Scholar
Chatzikonstantinou, A, Szabo, K, Ottomeyer, C, Kern, R, Hennerici, MG. Successive affection of bilateral temporomesial structures in a case of non-paraneoplastic limbic encephalitis demonstrated by serial MRI and FDG-PET. J Neurol 2009;256:1753–1755.Google Scholar
Baumgartner, A, Rauer, S, Mader, I, Meyer, PT. Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types. J Neurol 2013;260:2744–2753.Google Scholar
Kunze, A, Drescher, R, Kaiser, K, et al. Serial FDG PET/CT in autoimmune encephalitis with faciobrachial dystonic seizures. Clin Nucl Med 2014;39:e436–438.Google Scholar
Park, S, Choi, H, Cheon, GJ, Wook Kang, K, Lee, DS. 18F-FDG PET/CT in anti-LGI1 encephalitis: initial and follow-up findings. CLin Nucl Med 2015;40:156–158.Google Scholar
Serrano Vicente, J, Garcia Bernardo, L, Duran Barquero, C, et al. Brain metabolic changes in limbic encephalitis evidenced by 18FDG PET: correlation with symptomatology. Revista espanola de medicina nuclear e imagen molecular 2013;32:201–202.Google Scholar
Newey, CR, Sarwal, A, Hantus, S. [(18)F]-fluoro-deoxy-glucose positron emission tomography scan should be obtained early in cases of autoimmune encephalitis. Autoimmune Dis 2016;2016:9450452.Google Scholar
Chen, C, Wang, X, Zhang, C, et al. Seizure semiology in leucine-rich glioma-inactivated protein 1 antibody-associated limbic encephalitis. Epilepsy Behav 2017;77:90–95.Google Scholar
Dodich, A, Cerami, C, Iannaccone, S, et al. Neuropsychological and FDG-PET profiles in VGKC autoimmune limbic encephalitis. Brain Cogn 2016;108:81–87.Google Scholar
Shin, YW, Lee, ST, Shin, JW, et al. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. J Neuroimmunol 2013;265:75–81.Google Scholar
Tripathi, M, Tripathi, M, Roy, SG, et al. Metabolic topography of autoimmune non-paraneoplastic encephalitis. Neuroradiology 2018;60:189–198.Google Scholar
Jang, Y, Lee, ST, Bae, JY, et al. LGI1 expression and human brain asymmetry: insights from patients with LGI1-antibody encephalitis. J Neuroinflammation 2018;15:279.Google Scholar
d’Orsi, G, Martino, T, Lalla, A, et al. Faciobrachial dystonic seizures expressed as epileptic spasms, followed by focal seizures in anti-LGI1 encephalitis: a video-polygraphic study. Epileptic Disord 2018;20:525–529.Google Scholar
Shan, W, Liu, X, Wang, Q. Teaching neuroimages: (18)F-FDG-PET/SPM analysis in 3 different stages from a patient with LGI-1 autoimmune encephalitis. Neurology 2019;93:e1917–e1918.Google Scholar
Zuliani, L, Nosadini, M, Gastaldi, M, et al. Management of antibody-mediated autoimmune encephalitis in adults and children: literature review and consensus-based practical recommendations. Neurol Sci 2019;40:2017–2030.Google Scholar
Irani, SR, Gelfand, JM, Bettcher, BM, Singhal, NS, Geschwind, MD. Effect of rituximab in patients with leucine-rich, glioma-inactivated 1 antibody-associated encephalopathy. JAMA Neurol 2014;71:896–900.Google Scholar
Brown, JW, Martin, PJ, Thorpe, JW, et al. Long-term remission with rituximab in refractory leucine-rich glioma inactivated 1 antibody encephalitis. J Neuroimmunol 2014;271:66–68.Google Scholar
Abboud, H, Probasco, JC, Irani, S, et al. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry 2021;92:757–768.Google Scholar
Sola-Valls, N, Arino, H, Escudero, D, et al. Telemedicine assessment of long-term cognitive and functional status in anti-leucine-rich, glioma-inactivated 1 encephalitis. Neurol Neuroimmunol Neuroinflamm 2020;7:e652.Google Scholar
Miller, TD, Chong, TT, Aimola Davies, AM, et al. Human hippocampal CA3 damage disrupts both recent and remote episodic memories. Elife 2020;9:e41836.Google Scholar
Miller, TD, Chong, TT, Aimola Davies, AM, et al. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis. Brain 2017;140:1212–1219.Google Scholar
Xu, M, Bennett, DLH, Querol, LA, et al. Pain and the immune system: emerging concepts of IgG-mediated autoimmune pain and immunotherapies. J Neurol Neurosurg Psychiatry 2020;91:177–188.Google Scholar
Laurencin, C, Andre-Obadia, N, Camdessanche, JP, et al. Peripheral small fiber dysfunction and neuropathic pain in patients with Morvan syndrome. Neurology 2015;85:2076–2078.CrossRefGoogle ScholarPubMed
Lancaster, E, Huijbers, MG, Bar, V, et al. Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia. Ann Neurol 2011;69:303–311.Google Scholar
Giannoccaro, MP, Menassa, DA, Jacobson, L, et al. Behaviour and neuropathology in mice injected with human contactin-associated protein 2 antibodies. Brain 2019;142:2000–2012.Google Scholar
Pinatel, D, Hivert, B, Saint-Martin, M, et al. The Kv1-associated molecules TAG-1 and Caspr2 are selectively targeted to the axon initial segment in hippocampal neurons. J Cell Sci 2017;130:2209–2220.Google Scholar
Boyko, M, Au, KLK, Casault, C, de Robles, P, Pfeffer, G. Systematic review of the clinical spectrum of CASPR2 antibody syndrome. J Neurol 2020;267:1137–1146.Google Scholar
Joubert, B, Gobert, F, Thomas, L, et al. Autoimmune episodic ataxia in patients with anti-CASPR2 antibody-associated encephalitis. Neurol Neuroimmunol Neuroinflamm 2017;4:e371.Google Scholar
Govert, F, Witt, K, Erro, R, et al. Orthostatic myoclonus associated with Caspr2 antibodies. Neurology 2016;86:1353–1355.Google Scholar
van Sonderen, A, Arino, H, Petit-Pedrol, M, et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology 2016;87:521–528.Google Scholar
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;73:1115–1124.Google Scholar
Becker, EB, Zuliani, L, Pettingill, R, et al. Contactin-associated protein-2 antibodies in non-paraneoplastic cerebellar ataxia. J Neurol Neurosurg Psychiatry 2012;83:437–440.Google Scholar
Klockgether, T. Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol 2010;9:94–104.Google Scholar
Fabbri, M, Giannoccaro, MP, Leta, C, et al. Non-paraneoplastic ataxia in a patient with contactin-associated protein-2 antibodies and benign course. Eur J Neurol 2015;22:e62–63.Google Scholar
Melzer, N, Golombeck, KS, Gross, CC, Meuth, SG, Wiendl, H. Cytotoxic CD8+ T cells and CD138+ plasma cells prevail in cerebrospinal fluid in non-paraneoplastic cerebellar ataxia with contactin-associated protein-2 antibodies. J Neuroinflammation 2012;9:160.Google Scholar
Muñiz-Castrillo, S, Joubert, B, Elsensohn, MH, et al. Anti-CASPR2 clinical phenotypes correlate with HLA and immunological features. J Neurol Neurosurg Psychiatry 2020;91:1076–1084.Google Scholar
Malter, MP, Frisch, C, Schoene-Bake, JC, et al. Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity. J Neurol 2014;261:1695–1705.Google Scholar
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;12:157–165.Google Scholar
Scheibe, F, Ostendorf, L, Reincke, SM, et al. Daratumumab treatment for therapy-refractory anti-CASPR2 encephalitis. J Neurol 2020;267:317–323.Google Scholar
Walusinski, O, Honnorat, J. Augustin Morvan (1819–1897), a little-known rural physician and neurologist. Rev Neurol (Paris) 2013;169:2–8.Google Scholar
Serratrice, G, Azulay, JP. [What is left of Morvan’s fibrillary chorea?]. Rev Neurol (Paris) 1994;150:257–265.Google Scholar
Barber, PA, Anderson, NE, Vincent, A. Morvan’s syndrome associated with voltage-gated K+ channel antibodies. Neurology 2000;54:771–772.Google Scholar
Cottrell, DA, Blackmore, KJ, Fawcett, PR, et al. Sub-acute presentation of Morvan’s syndrome after thymectomy. J Neurol Neurosurg Psychiatry 2004;75:1504–1505.Google Scholar
Lee, EK, Maselli, RA, Ellis, WG, Agius, MA. Morvan’s fibrillary chorea: a paraneoplastic manifestation of thymoma. J Neurol Neurosurg Psychiatry 1998;65:857–862.Google Scholar
Josephs, KA, Silber, MH, Fealey, RD, et al. Neurophysiologic studies in Morvan syndrome. J Clin Neurophysiol 2004;21:440–445.Google Scholar
Abou-Zeid, E, Boursoulian, LJ, Metzer, WS, Gundogdu, B. Morvan syndrome: a case report and review of the literature. J Clin Neuromuscul Dis 2012;13:214–227.Google Scholar
Lugaresi, E, Provini, F. Agrypnia excitata: clinical features and pathophysiological implications. Sleep Med Rev 2001;5:313–322.Google Scholar
Provini, F, Marconi, S, Amadori, M, et al. Morvan chorea and agrypnia excitata: when video-polysomnographic recording guides the diagnosis. Sleep Med 2011;12:1041–1043.Google Scholar
Lugaresi, E, Provini, F, Cortelli, P. Agrypnia excitata. Sleep Med 2011;12(Suppl. 2):S3–10.Google Scholar
Madrid, A, Gil-Peralta, A, Gil-Neciga, E, Gonzalez, JR, Jarrin, S. Morvan’s fibrillary chorea: remission after plasmapheresis. J Neurol 1996;243:350–353.Google Scholar
van den Berg, JS, Van Engelen, BG, Boerman, RH, De Baets, MH. Acquired neuromyotonia: superiority of plasma exchange over high-dose intravenous human immunoglobulin. J Neurol 1999;246:623–625.Google Scholar
Ishii, A, Hayashi, A, Ohkoshi, N, et al. Clinical evaluation of plasma exchange and high dose intravenous immunoglobulin in a patient with Isaacs’ syndrome [see comments]. J Neurol Neurosurg Psychiatry 1994;57:840–842.Google Scholar
Fischer-Perroudon, C, Trillet, M, Mouret, J, et al. [Polygraphic and metabolic studies of persistent insomnia with hallucinations. Apropos of an antomo-clinical study of a case of Morvan’s fibrillar chorea]. Rev Neurol (Paris) 1974;130:111–125.Google Scholar
Patterson, KR, Dalmau, J, Lancaster, E. Mechanisms of Caspr2 antibodies in autoimmune encephalitis and neuromyotonia. Ann Neurol 2018;83:40–51.Google Scholar
Ong, E, Viaccoz, A, Ducray, F, et al. Dramatic improvement after rituximab in a patient with paraneoplastic treatment-refractory Morvan syndrome associated with anti-CASPR2 antibodies. Eur J Neurol 2013;20:e96–97.Google Scholar
Lopez-Chiriboga, AS, Klein, C, Zekeridou, A, et al. LGI1 and CASPR2 neurological autoimmunity in children. Ann Neurol 2018;84:473–480.Google Scholar
Zhang, J, Ji, T, Chen, Q, et al. Pediatric autoimmune encephalitis: case series from two Chinese tertiary pediatric neurology centers. Front Neurol 2019;10:906.Google Scholar
Nosadini, M, Toldo, I, Tascini, B, et al. LGI1 and CASPR2 autoimmunity in children: systematic literature review and report of a young girl with Morvan syndrome. J Neuroimmunol 2019;335:577008.Google Scholar
Wright, S, Geerts, AT, Jol-van der Zijde, CM, et al. Neuronal antibodies in pediatric epilepsy: clinical features and long-term outcomes of a historical cohort not treated with immunotherapy. Epilepsia 2016;57:823–831.Google Scholar
Suleiman, J, Wright, S, Gill, D, et al. Autoantibodies to neuronal antigens in children with new-onset seizures classified according to the revised ILAE organization of seizures and epilepsies. Epilepsia 2013;54:2091–2100.Google Scholar
Garcia-Tarodo, S, Datta, AN, Ramelli, GP, et al. Circulating neural antibodies in unselected children with new-onset seizures. Eur J Paediatr Neurol 2018;22:396–403.Google Scholar
Borusiak, P, Bettendorf, U, Wiegand, G, et al. Autoantibodies to neuronal antigens in children with focal epilepsy and no prima facie signs of encephalitis. Eur J Paediatr Neurol 2016;20:573–579.Google Scholar
Tekturk, P, Baykan, B, Erdag, E, et al. Investigation of neuronal auto-antibodies in children diagnosed with epileptic encephalopathy of unknown cause. Brain Dev 2018;40:909–917.Google Scholar
Syrbe, S, Stettner, GM, Bally, J, et al. CASPR2 autoimmunity in children expanding to mild encephalopathy with hypertension. Neurology 2020;94:e2290–e2301.Google Scholar

Accessibility standard: Unknown

Accessibility compliance for the PDF of this book is currently unknown and may be updated in the future.

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×