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-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-16T17:01:19.655Z Has data issue: false hasContentIssue false

Chapter 23 - Immunity, Inflammation, and Epilepsy

from Section 4 - Autoimmunity in Neurological and Psychiatric 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

In this chapter we review the inflammatory mechanisms involved in epileptogenesis, the caveats and limitations of the term autoimmune epilepsy, and two epileptic syndromes of autoimmune origin: epilepsy associated with GAD antibodies and Rasmussen encephalitis. The International League Against Epilepsy (ILAE) recently proposed the definition of acute symptomatic seizures secondary to autoimmune encephalitis for the seizures that occur in the setting of the active phase of immune-mediated encephalitis. In contrast, the term autoimmune epilepsy applies to chronic seizures considered to be secondary to autoimmune brain diseases. If promptly diagnosed and treated, patients with symptomatic seizures due to antibody-mediated encephalitis rarely evolve to develop epilepsy and, therefore, they do not fulfil criteria of autoimmune epilepsy. Scoring systems to predict autoimmune seizures are not very useful because they rely on the presence of additional neurological manifestations or diagnostic tests included in the definition of autoimmune encephalitis. Antibodies against neuronal surface antigens occur in a minority (<5%) of patients with isolated epilepsy; the significance of these antibodies is unclear as the spectrum of symptoms of these patients is not different from that of seronegative cases. In contrast, antibodies against GAD (an intracellular protein) occur in a small subset of patients with temporal lobe epilepsy that is usually refractory to anti-seizure medication.

Keywords

Autoimmune seizuresautoimmune epilepsyGAD antibodiesRasmussen encephalitisautoimmune encephalitis
Type
Chapter
Information
Autoimmune Encephalitis and Related Disorders of the Nervous System , pp. 588 - 610
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.)

References

Scheffer, IE, Berkovic, S, Capovilla, G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017;58:512–521.CrossRefGoogle ScholarPubMed
Marchi, N, Granata, T, Janigro, D. Inflammatory pathways of seizure disorders. Trends Neurosci 2014;37:55–65.CrossRefGoogle ScholarPubMed
Vezzani, A, Balosso, S, Ravizza, T. Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy. Nat Rev Neurol 2019;15:459–472.CrossRefGoogle ScholarPubMed
Xu, JH, Long, L, Tang, YC, et al. CCR3, CCR2A and macrophage inflammatory protein (MIP)-1a, monocyte chemotactic protein-1 (MCP-1) in the mouse hippocampus during and after pilocarpine-induced status epilepticus (PISE). Neuropathol Appl Neurobiol 2009;35:496–514.Google Scholar
Riazi, K, Galic, MA, Pittman, QJ. Contributions of peripheral inflammation to seizure susceptibility: cytokines and brain excitability. Epilepsy Res 2010;89:34–42.CrossRefGoogle ScholarPubMed
Hirsch, LJ, Gaspard, N, van Baalen, A, et al. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia 2018;59:739–744.Google Scholar
Geis, C, Planaguma, J, Carreño, M, Graus, F, Dalmau, J. Autoimmune seizures and epilepsy. J Clin Invest 2019;129:926–940.Google Scholar
Glass, CK, Saijo, K, Winner, B, Marchetto, MC, Gage, FH. Mechanisms underlying inflammation in neurodegeneration. Cell 2010;140:918–934.Google Scholar
Ransohoff, RM, Engelhardt, B. The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol 2012;12:623–635.Google Scholar
Galic, MA, Riazi, K, Pittman, QJ. Cytokines and brain excitability. Front Neuroendocrinol 2012;33:116–125.Google Scholar
Jun, JS, Lee, ST, Kim, R, Chu, K, Lee, SK. Tocilizumab treatment for new onset refractory status epilepticus. Ann Neurol 2018;84:940–945.Google Scholar
Uludag, IF, Duksal, T, Tiftikcioglu, BI, et al. IL-1beta, IL-6 and IL1Ra levels in temporal lobe epilepsy. Seizure 2015;26:22–25.Google Scholar
Crespel, A, Coubes, P, Rousset, MC, et al. Inflammatory reactions in human medial temporal lobe epilepsy with hippocampal sclerosis. Brain Res 2002;952:159–169.Google Scholar
Ravizza, T, Gagliardi, B, Noe, F, et al. Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy. Neurobiol Dis 2008;29:142–160.Google Scholar
Vezzani, A, Granata, T. Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 2005;46:1724–1743.CrossRefGoogle ScholarPubMed
Dube, CM, Ravizza, T, Hamamura, M, et al. Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers. J Neurosci 2010;30:7484–7494.Google Scholar
Roseti, C, van Vliet, EA, Cifelli, P, et al. GABAA currents are decreased by IL-1beta in epileptogenic tissue of patients with temporal lobe epilepsy: implications for ictogenesis. Neurobiol Dis 2015;82:311–320.Google Scholar
Kenney-Jung, DL, Vezzani, A, Kahoud, RJ, et al. Febrile infection-related epilepsy syndrome treated with anakinra. Ann Neurol 2016;80:939–945.Google Scholar
Vezzani, A, Moneta, D, Conti, M, et al. Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice. Proc Natl Acad Sci USA 2000;97:11534–11539.Google Scholar
Gilmore, TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 2006;25:6680–6684.Google Scholar
O’Neill, LA, Kaltschmidt, C. NF-kappa B: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci 1997;20:252–258.Google Scholar
Balosso, S, Maroso, M, Sanchez-Alavez, M, et al. A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1beta. Brain 2008;131:3256–3265.Google Scholar
Ravizza, T, Terrone, G, Salamone, A, et al. High Mobility Group Box 1 is a novel pathogenic factor and a mechanistic biomarker for epilepsy. Brain Behav Immun 2018;72:14–21.Google Scholar
Cacheaux, LP, Ivens, S, David, Y, et al. Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis. J Neurosci 2009;29:8927–8935.Google Scholar
Vezzani, A, French, J, Bartfai, T, Baram, TZ. The role of inflammation in epilepsy. Nat Rev Neurol 2011;7:31–40.Google Scholar
Cerri, C, Caleo, M, Bozzi, Y. Chemokines as new inflammatory players in the pathogenesis of epilepsy. Epilepsy Res 2017;136:77–83.CrossRefGoogle ScholarPubMed
Fabene, PF, Laudanna, C, Constantin, G. Leukocyte trafficking mechanisms in epilepsy. Molec Immunol 2013;55:100–104.Google Scholar
Cerri, C, Genovesi, S, Allegra, M, et al. The chemokine CCL2 mediates the seizure-enhancing effects of systemic inflammation. J Neurosci 2016;36:3777–3788.Google Scholar
Boer, K, Jansen, F, Nellist, M, et al. Inflammatory processes in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex. Epilepsy Res 2008;78:7–21.Google Scholar
Iyer, A, Zurolo, E, Spliet, WG, et al. Evaluation of the innate and adaptive immunity in type I and type II focal cortical dysplasias. Epilepsia 2010;51:1763–1773.Google Scholar
Owens, GC, Garcia, AJ, Mochizuki, AY, et al. Evidence for innate and adaptive immune responses in a cohort of intractable pediatric epilepsy surgery patients. Front Immunol 2019;10:121.Google Scholar
Xu, D, Robinson, AP, Ishii, T, et al. Peripherally derived T regulatory and gammadelta T cells have opposing roles in the pathogenesis of intractable pediatric epilepsy. J Exp Med 2018;215:1169–1186.Google Scholar
Levite, M. Autoimmune epilepsy. Nat Immunol 2002;3:500.Google Scholar
Palace, J, Lang, B. Epilepsy: an autoimmune disease? J Neurol Neurosurg Psychiatry 2000;69:711–714.Google Scholar
Rasmussen, T, Olszewski, J, Lloydsmith, D. Focal seizures due to chronic localized encephalitis. Neurology 1958;8:435–445.Google Scholar
Mihailovic, LT, Cupic, D. Epileptiform activity evoked by intracerebral injection of anti-brain antibodies. Brain Res 1971;32:97–124.Google Scholar
Bowen, FP, Kosarova, J, Casella, D, Nicklas, WJ, Berl, S. Focal epileptogenic activity induced by topical application of antisera to brain actomyosin-like protein. Brain Res 1976;102:363–367.Google Scholar
Karpiak, SE Jr, Bowen, FP, Rapport, MM. Epileptiform activity induced by antiserum to synaptic membrane. Brain Res 1973;59:303–310.Google Scholar
Dalmau, J, Graus, F, Rosenblum, MK, Posner, JB. Anti-Hu–associated paraneoplastic encephalomyelitis/sensory neuronopathy: a clinical study of 71 patients. Medicine (Baltimore) 1992;71:59–72.Google Scholar
Solimena, M, Folli, F, Denis-Donini, S, et al. Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N Engl J Med 1988;318:1012–1020.Google Scholar
Giometto, B, Nicolao, P, Macucci, M, et al. Temporal-lobe epilepsy associated with glutamic-acid-decarboxylase autoantibodies. Lancet 1998;352:457.Google Scholar
Karpiak, SE, Huang, YL, Rapport, MM. Immunological model of epilepsy: epileptiform activity induced by fragments of antibody to GM1 ganglioside. J Neuroimmunol 1982;3:15–21.Google Scholar
Karpiak, SE, Mahadik, SP, Graf, L, Rapport, MM. An immunological model of epilepsy: seizures induced by antibodies to GM1 ganglioside. Epilepsia 1981;22:189–196.Google Scholar
Bartolomei, F, Boucraut, J, Barrie, M, et al. Cryptogenic partial epilepsies with anti-GM1 antibodies: a new form of immune-mediated epilepsy? Epilepsia 1996;37:922–926.Google Scholar
McKnight, K, Jiang, Y, Hart, Y, et al. Serum antibodies in epilepsy and seizure-associated disorders. Neurology 2005;65:1730–1736.CrossRefGoogle ScholarPubMed
Rogers, SW, Andrews, PI, Gahring, LC, et al. Autoantibodies to glutamate receptor GluR3 in Rasmussen’s encephalitis. Science 1994;265:648–651.CrossRefGoogle ScholarPubMed
Wiendl, H, Bien, CG, Bernasconi, P, et al. GluR3 antibodies: prevalence in focal epilepsy but no specificity for Rasmussen’s encephalitis. Neurology 2001;57:1511–1514.Google Scholar
Mantegazza, R, Bernasconi, P, Baggi, F, et al. Antibodies against GluR3 peptides are not specific for Rasmussen’s encephalitis but are also present in epilepsy patients with severe, early onset disease and intractable seizures. J Neuroimmunol 2002;131:179–185.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.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.CrossRefGoogle ScholarPubMed
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
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
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
Dalmau, J, Graus, F. Antibody-mediated encephalitis. N Engl J Med 2018;378:840–851.Google Scholar
Dalmau, J, Geis, C, 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
Gaspard, N. Autoimmune epilepsy. Continuum (Minneapolis, Minn) 2016;22:227–245.Google Scholar
Toledano, M, Pittock, SJ. Autoimmune epilepsy. Semin Neurol 2015;35:245–258.Google Scholar
Husari, KS, Dubey, D. Autoimmune epilepsy. Neurotherapeutics 2019;16:685–702.Google Scholar
Quek, AML, O’Toole, O. Autoimmune epilepsy: the evolving science of neural autoimmunity and its impact on epilepsy management. Semin Neurol 2018;38:290–302.Google Scholar
Greco, A, Rizzo, MI, De Virgilio, A, et al. Autoimmune epilepsy. Autoimmunity Rev 2016;15:221–225.Google Scholar
Irani, SR, Bien, CG, Lang, B. Autoimmune epilepsies. Curr Opin Neurol 2011;24:146–153.Google Scholar
Fisher, RS, Acevedo, C, Arzimanoglou, A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014;55:475–482.Google Scholar
Steriade, C, Britton, J, Dale, RC, et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune-associated epilepsy: conceptual definitions. Epilepsia 2020;61:1341–1351.Google Scholar
Spatola, M, Dalmau, J. Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Curr Opin Neurol 2017;30:345–353.Google Scholar
de Bruijn, M, van Sonderen, A, van Coevorden-Hameete, MH, et al. Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis. Neurology 2019;92:e2185–e2196.Google Scholar
Beghi, E, Carpio, A, Forsgren, L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia 2010;51:671–675.Google Scholar
Shavit, YB, Graus, F, Probst, A, Rene, R, Steck, AJ. Epilepsia partialis continua: a new manifestation of anti-Hu-associated paraneoplastic encephalomyelitis. Ann Neurol 1999;45:255–258.Google Scholar
Carreño, M, Bien, CG, Asadi-Pooya, AA, et al. Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies. Epilepsy Res 2017;129:101–105.Google Scholar
Fadul, CE, Stommel, EW, Dragnev, KH, Eskey, CJ, Dalmau, JO. Focal paraneoplastic limbic encephalitis presenting as orgasmic epilepsy. J Neurooncol 2005;72:195–198.Google Scholar
Daif, A, Lukas, RV, Issa, NP, et al. Antiglutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy. Epilepsy Behav 2018;80:331–336.Google Scholar
Mut, M, Schiff, D, Dalmau, J. Paraneoplastic recurrent multifocal encephalitis presenting with epilepsia partialis continua. J Neurooncol 2005;72:63–66.CrossRefGoogle ScholarPubMed
Kinirons, P, O’Dwyer, JP, Connolly, S, Hutchinson, M. Paraneoplastic limbic encephalitis presenting as lingual epilepsia partialis continua. J Neurol 2006;253:256–257.Google Scholar
Llado, A, Carpentier, AF, Honnorat, J, et al. Hu-antibody-positive patients with or without cancer have similar clinical profiles. J Neurol Neurosurg Psychiatry 2006;77:996–997.Google Scholar
Liimatainen, S, Peltola, M, Sabater, L, et al. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia 2010;51:760–767.Google Scholar
Symonds, JD, Moloney, TC, Lang, B, et al. Neuronal antibody prevalence in children with seizures under 3 years: a prospective national cohort. Neurology 2020;95:e1590–e1598.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
Veri, K, Uibo, O, Talvik, T, et al. Newly-diagnosed pediatric epilepsy is associated with elevated autoantibodies to glutamic acid decarboxylase but not cardiolipin. Epilepsy Res 2013;105:86–91.Google Scholar
von Podewils, F, Suesse, M, Geithner, J, et al. Prevalence and outcome of late-onset seizures due to autoimmune etiology: a prospective observational population-based cohort study. Epilepsia 2017;58:1542–1550.Google Scholar
Nobrega, AW Jr, Gregory, CP, Schlindwein-Zanini, R, et al. Mesial temporal lobe epilepsy with hippocampal sclerosis is infrequently associated with neuronal autoantibodies. Epilepsia 2018;59:e152–e156.Google Scholar
Ekizoglu, E, Tuzun, E, Woodhall, M, et al. Investigation of neuronal autoantibodies in two different focal epilepsy syndromes. Epilepsia 2014;55:414–422.Google Scholar
Vanli-Yavuz, EN, Erdag, E, Tuzun, E, et al. Neuronal autoantibodies in mesial temporal lobe epilepsy with hippocampal sclerosis. J Neurol Neurosurg Psychiatry 2016;87:684–692.Google Scholar
Gozubatik-Celik, G, Ozkara, C, Ulusoy, C, et al. Anti-neuronal autoantibodies in both drug responsive and resistant focal seizures with unknown cause. Epilepsy Res 2017;135:131–136.Google Scholar
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
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.Google Scholar
Dubey, D, Alqallaf, A, Hays, R, et al. Neurological autoantibody prevalence in epilepsy of unknown etiology. JAMA Neurol 2017;74:397–402.Google Scholar
Iorio, R, Assenza, G, Tombini, M, et al. The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy. Eur J Neurol 2015;22:70–78.Google Scholar
Baysal-Kirac, L, Tuzun, E, Erdag, E, et al. Neuronal autoantibodies in epilepsy patients with peri-ictal autonomic findings. J Neurol 2016;263:455–466.Google Scholar
Errichiello, L, Perruolo, G, Pascarella, A, et al. Autoantibodies to glutamic acid decarboxylase (GAD) in focal and generalized epilepsy: a study on 233 patients. J Neuroimmunol 2009;211:120–123.Google Scholar
Tecellioglu, M, Kamisli, O, Kamisli, S, Yucel, FE, Ozcan, C. Neurological autoantibodies in drug-resistant epilepsy of unknown cause. Irish J Med Sci 2018;187:1057–1063.Google Scholar
Tizazu, E, Ellis, CA, Reichert, J, Lancaster, E. Low rate of glutamic acid decarboxylase 65 (GAD-65) antibodies in chronic epilepsy. Seizure 2020;80:38–41.Google Scholar
Falip, M, Carreño, M, Miro, J, et al. Prevalence and immunological spectrum of temporal lobe epilepsy with glutamic acid decarboxylase antibodies. Eur J Neurol 2012;19:827–833.Google Scholar
Lilleker, JB, Biswas, V, Mohanraj, R. Glutamic acid decarboxylase (GAD) antibodies in epilepsy: diagnostic yield and therapeutic implications. Seizure 2014;23:598–602.Google Scholar
Graus, F, Gorman, MP. Voltage-gated potassium channel antibodies: game over. Neurology 2016;86:1657–1658.Google Scholar
Swayne, A, Tjoa, L, Broadley, S, et al. Antiglycine receptor antibody related disease: a case series and literature review. Eur J Neurol 2018;25:1290–1298.CrossRefGoogle ScholarPubMed
Martinez-Hernandez, E, Sepulveda, M, Rostasy, K, et al. Antibodies to aquaporin 4, myelin-oligodendrocyte glycoprotein, and the glycine receptor alpha1 subunit in patients with isolated optic neuritis. JAMA Neurol 2015;72:187–193.Google Scholar
Armangue, T, Sabater, L, Torres-Vega, E, et al. Clinical and immunological features of opsoclonus-myoclonus syndrome in the era of neuronal cell surface antibodies. JAMA Neurol 2016;73:417–424.Google Scholar
Bozzetti, S, Rossini, F, Ferrari, S, et al. Epileptic seizures of suspected autoimmune origin: a multicentre retrospective study. J Neurol Neurosurg Psychiatry 2020;91:1145–1153.Google Scholar
Spatola, M, Petit-Pedrol, M, Simabukuro, MM, et al. Investigations in GABAA receptor antibody-associated encephalitis. Neurology 2017;88:1012–1020.Google Scholar
Maureille, A, Fenouil, T, Joubert, B, et al. Isolated seizures are a common early feature of paraneoplastic anti-GABAB receptor encephalitis. J Neurol 2019;266:195–206.CrossRefGoogle 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
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
Irani, SR, Buckley, C, Vincent, A, et al. Immunotherapy-responsive seizure-like episodes with potassium channel antibodies. Neurology 2008;71:1647–1648.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
Rocamora, R, Becerra, JL, Fossas, P, et al. Pilomotor seizures: an autonomic semiology of limbic encephalitis? Seizure 2014;23:670–673.Google Scholar
Aurangzeb, S, Symmonds, M, Knight, RK, et al. LGI1-antibody encephalitis is characterised by frequent, multifocal clinical and subclinical seizures. Seizure 2017;50:14–17.Google Scholar
Gillinder, L, Tjoa, L, Mantzioris, B, Blum, S, Dionisio, S. Refractory chronic epilepsy associated with neuronal auto-antibodies: could perisylvian semiology be a clue? Epileptic Disord 2017;19:439–449.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.Google Scholar
Quek, AM, Britton, JW, McKeon, A, et al. Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol 2012;69:582–593.Google Scholar
Dubey, D, Singh, J, Britton, JW, et al. Predictive models in the diagnosis and treatment of autoimmune epilepsy. Epilepsia 2017;58:1181–1189.Google Scholar
Britton, J. Autoimmune epilepsy. Handb Clin Neurol 2016;133:219–245.Google Scholar
Suleiman, J, Dale, RC. The recognition and treatment of autoimmune epilepsy in children. Dev Med Child Neurol 2015;57:431–440.Google Scholar
Dubey, D, Kothapalli, N, McKeon, A, et al. Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction. J Neuroimmunol 2018;323:62–72.Google Scholar
Mattozzi, S, Sabater, L, Escudero, D, et al. Hashimoto encephalopathy in the 21st century. Neurology 2020;94:e217–e224.Google Scholar
Dubey, D, Pittock, SJ, McKeon, A. Antibody prevalence in epilepsy and encephalopathy score: increased specificity and applicability. Epilepsia 2019;60:367–369.Google Scholar
de Bruijn, MAAM, Bastiaansen, AEM, Mojzisova, H, et al. Antibodies contributing to focal epilepsy signs and symptoms score. Ann Neurol 2021;89:698–710.Google Scholar
Troscher, AR, Wimmer, I, Quemada-Garrido, L, et al. Microglial nodules provide the environment for pathogenic T cells in human encephalitis. Acta Neuropathol 2019;137:619–635.Google Scholar
Bien, CG, Widman, G, Urbach, H, et al. The natural history of Rasmussen’s encephalitis. Brain 2002;125:1751–1759.Google Scholar
Granata, T, Gobbi, G, Spreafico, R, et al. Rasmussen’s encephalitis: early characteristics allow diagnosis. Neurology 2003;60:422–425.Google Scholar
Andermann, F. Rasmussen Syndrome and movement disorder. Mov Disord 2002;17:437–438.Google Scholar
Bien, CG, Elger, CE, Leitner, Y, et al. Slowly progressive hemiparesis in childhood as a consequence of Rasmussen encephalitis without or with delayed-onset seizures. Eur J Neurol 2007;14:387–390.Google Scholar
Carreño, M, Marti, MJ, Aldecoa, I, et al. Unilateral pallidal stimulation for disabling dystonia due to Rasmussen’s disease. J Neurol Neurosurg Psychiatry 2019;90:108–110.Google Scholar
Dupont, S, Gales, A, Sammey, S, Vidailhet, M, Lambrecq, V. Late-onset Rasmussen encephalitis: a literature appraisal. Autoimmunity Rev 2017;16:803–810.Google Scholar
Rasmussen, T. Further observations on the syndrome of chronic encephalitis and epilepsy. Appl Neurophysiol 1978;41:1–12.Google Scholar
Bien, CG, Granata, T, Antozzi, C, et al. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain 2005;128:454–471.Google Scholar
Chiapparini, L, Granata, T, Farina, L, et al. Diagnostic imaging in 13 cases of Rasmussen’s encephalitis: can early MRI suggest the diagnosis? Neuroradiology 2003;45:171–183.Google Scholar
Wagner, J, Schoene-Bake, JC, Bien, CG, et al. Automated 3D MRI volumetry reveals regional atrophy differences in Rasmussen encephalitis. Epilepsia 2012;53:613–621.Google Scholar
David, B, Prillwitz, CC, Hoppe, C, et al. Morphometric MRI findings challenge the concept of the ‘unaffected’ hemisphere in Rasmussen encephalitis. Epilepsia 2019;60:e40–e46.CrossRefGoogle ScholarPubMed
Lee, JS, Juhasz, C, Kaddurah, AK, Chugani, HT. Patterns of cerebral glucose metabolism in early and late stages of Rasmussen’s syndrome. J Child Neurol 2001;16:798–805.Google Scholar
Pardo, CA, Vining, EP, Guo, L, et al. The pathology of Rasmussen syndrome: stages of cortical involvement and neuropathological studies in 45 hemispherectomies. Epilepsia 2004;45:516–526.Google Scholar
Varadkar, S, Bien, CG, Kruse, CA, et al. Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances. Lancet Neurol 2014;13:195–205.Google Scholar
Olson, HE, Lechpammer, M, Prabhu, SP, et al. Clinical application and evaluation of the Bien diagnostic criteria for Rasmussen encephalitis. Epilepsia 2013;54:1753–1760.Google Scholar
Armangue, T, Spatola, M, Vlagea, A, 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;17:760–772.CrossRefGoogle ScholarPubMed
Bauer, J, Elger, CE, Hans, VH, et al. Astrocytes are a specific immunological target in Rasmussen’s encephalitis. Ann Neurol 2007;62:67–80.Google Scholar
Bien, CG, Bauer, J, Deckwerth, TL, et al. Destruction of neurons by cytotoxic T cells: a new pathogenic mechanism in Rasmussen’s encephalitis. Ann Neurol 2002;51:311–318.Google Scholar
Schneider-Hohendorf, T, Mohan, H, Bien, CG, et al. CD8(+) T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing. Nat Commun 2016;7:11153.Google Scholar
Schwab, N, Bien, CG, Waschbisch, A, et al. CD8+ T-cell clones dominate brain infiltrates in Rasmussen encephalitis and persist in the periphery. Brain 2009;132:1236–1246.Google Scholar
Granata, T, Cross, H, Theodore, W, Avanzini, G. Immune-mediated epilepsies. Epilepsia 2011;52(Suppl. 3):5–11.Google Scholar
Browner, N, Azher, SN, Jankovic, J. Botulinum toxin treatment of facial myoclonus in suspected Rasmussen encephalitis. Mov Disord 2006;21:1500–1502.Google Scholar
Granata, T, Fusco, L, Gobbi, G, et al. Experience with immunomodulatory treatments in Rasmussen’s encephalitis. Neurology 2003;61:1807–1810.Google Scholar
Thilo, B, Stingele, R, Knudsen, K, et al. A case of Rasmussen encephalitis treated with rituximab. Nat Rev Neurol 2009;5:458–462.Google Scholar
Daniel, RT, Villemure, JG. Hemispherotomy techniques. J Neurosurg 2003;98:438–439.Google Scholar
Jonas, R, Nguyen, S, Hu, B, et al. Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes. Neurology 2004;62:1712–1721.Google Scholar
Cay-Martinez, KC, Hickman, RA, McKhann Ii, GM, Provenzano, FA, Sands, TT. Rasmussen encephalitis: an update. Semin Neurol 2020;40:201–210.Google Scholar
Bien, CG, Schramm, J. Treatment of Rasmussen encephalitis half a century after its initial description: promising prospects and a dilemma. Epilepsy Res 2009;86:101–112.CrossRefGoogle ScholarPubMed
Bien, CG, Tiemeier, H, Sassen, R, et al. Rasmussen encephalitis: incidence and course under randomized therapy with tacrolimus or intravenous immunoglobulins. Epilepsia 2013;54:543–550.Google Scholar
Hart, YM, Cortez, M, Andermann, F, et al. Medical treatment of Rasmussen’s syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients. Neurology 1994;44:1030–1036.Google Scholar
Bahi-Buisson, N, Villanueva, V, Bulteau, C, et al. Long term response to steroid therapy in Rasmussen encephalitis. Seizure 2007;16:485–492.Google Scholar
Villani, F, Spreafico, R, Farina, L, et al. Positive response to immunomodulatory therapy in an adult patient with Rasmussen’s encephalitis. Neurology 2001;56:248–250.Google Scholar
Chinchilla, D, Dulac, O, Robain, O, et al. Reappraisal of Rasmussen’s syndrome with special emphasis on treatment with high doses of steroids. J Neurol Neurosurg Psychiatry 1994;57:1325–1333.Google Scholar
Bittner, S, Simon, OJ, Gobel, K, et al. Rasmussen encephalitis treated with natalizumab. Neurology 2013;81:395–397.Google Scholar
Liba, Z, Sedlacek, P, Sebronova, V, et al. Alemtuzumab and intrathecal methotrexate failed in the therapy of Rasmussen encephalitis. Neurol Neuroimmunol Neuroinflamm 2017;4:e354.Google Scholar
Lagarde, S, Villeneuve, N, Trébuchon, A, et al. Anti-tumor necrosis factor alpha therapy (adalimumab) in Rasmussen’s encephalitis: an open pilot study. Epilepsia 2016;57:956–966.Google Scholar
Bu, DF, Erlander, MG, Hitz, BC, et al. Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Proc Natl Acad Sci USA 1992;89:2115–2119.Google Scholar
Ellis, TM, Atkinson, MA. The clinical significance of an autoimmune response against glutamic acid decarboxylase. Nat Med 1996;2:148–153.Google Scholar
Baekkeskov, S. Immunoreactivity to a 64,000 Mr human islet cell antigen in sera from insulin-dependent diabetes mellitus patients and individuals with abnormal glucose tolerance. Molec Biol Med 1986;3:137–142.Google Scholar
Meinck, HM, Faber, L, Morgenthaler, N, et al. Antibodies against glutamic acid decarboxylase: prevalence in neurological diseases. J Neurol Neurosurg Psychiatry 2001;71:100–103.Google Scholar
Saiz, A, Blanco, Y, Sabater, L, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain 2008;131:2553–2563.Google Scholar
Graus, F, Saiz, A, Dalmau, J. GAD antibodies in neurological disorders: insights and challenges. Nat Rev Neurol 2020;16:353–365.Google Scholar
Walikonis, JE, Lennon, VA. Radioimmunoassay for glutamic acid decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus. Mayo Clin Proc 1998;73:1161–1166.Google Scholar
Peltola, J, Kulmala, P, Isojarvi, J, et al. Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy. Neurology 2000;55:46–50.Google Scholar
Dalakas, MC, Li, M, Fujii, M, Jacobowitz, DM. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology 2001;57:780–784.Google Scholar
Malter, MP, Helmstaedter, C, Urbach, H, Vincent, A, Bien, CG. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol 2010;67:470–478.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
Malter, MP, Frisch, C, Zeitler, H, et al. Treatment of immune-mediated temporal lobe epilepsy with GAD antibodies. Seizure 2015;30:57–63.Google Scholar
Arino, H, Hoftberger, R, Gresa-Arribas, N, et al. Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol 2015;72:874–881.Google Scholar
Sharma, A, Dubey, D, Sawhney, A, Janga, K. GAD65 positive autoimmune limbic encephalitis: a case report and review of literature. J Clin Med Res 2012;4:424–428.Google Scholar
Blanc, F, Ruppert, E, Kleitz, C, et al. Acute limbic encephalitis and glutamic acid decarboxylase antibodies: a reality? J Neurol Sci 2009;287:69–71.Google Scholar
Boronat, A, Sabater, L, Saiz, A, Dalmau, J, Graus, F. GABAB receptor antibodies in limbic encephalitis and anti-GAD-associated neurologic disorders. Neurology 2011;76:795–800.Google Scholar
Widman, G, Golombeck, K, Hautzel, H, et al. Treating a GAD65 antibody-associated limbic encephalitis with basiliximab: a case study. Front Neurol 2015;6:167.Google Scholar
Khawaja, AM, Vines, BL, Miller, DW, Szaflarski, JP, Amara, AW. Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes. Epileptic Disord 2016;18:34–43.Google Scholar
Nair, DR, Laxer, KD, Weber, PB, et al. Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy. Neurology 2020;95:e1244–e1256.Google Scholar
Feyissa, AM, Mirro, EA, Wabulya, A, et al. Brain-responsive neurostimulation treatment in patients with GAD65 antibody-associated autoimmune mesial temporal lobe epilepsy. Epilepsia Open 2020;5:307–313.Google Scholar
Chou, IC, Wang, CH, Lin, WD, et al. Risk of epilepsy in type 1 diabetes mellitus: a population-based cohort study. Diabetologia 2016;59:1196–1203.Google Scholar
Ho, MS, Weller, NJ, Ives, FJ, et al. Prevalence of structural central nervous system abnormalities in early-onset type 1 diabetes mellitus. J Pediatr 2008;153:385–390.Google Scholar
Falip, M, Miro, J, Carreño, M, et al. Hypoglycemic seizures and epilepsy in type I diabetes mellitus. J Neurol Sci 2014;346:307–309.Google Scholar
Watad, A, Tiosano, S, Bragazzi, NL, et al. Epilepsy among systemic lupus erythematosus patients: insights from a large database analysis. Neuroepidemiology 2018;50:1–6.Google Scholar
Andrade, RM, Alarcon, GS, Gonzalez, LA, et al. Seizures in patients with systemic lupus erythematosus: data from LUMINA, a multiethnic cohort (LUMINA LIV). Ann Rheumat Dis 2008;67:829–834.Google Scholar
Tsai, JD, Lin, CL, Lin, CC, Sung, FC, Lue, KH. Risk of epilepsy in patients with systemic lupus erythematosus: a retrospective cohort study. Neuropsychiatric Dis Treat 2014;10:1635–1643.Google Scholar
Fleetwood, T, Cantello, R, Comi, C. Antiphospholipid syndrome and the neurologist: from pathogenesis to therapy. Front Neurol 2018;9:1001.Google Scholar
DeGiorgio, LA, Konstantinov, KN, Lee, SC, et al. A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 2001;7:1189–1193.Google Scholar
Tay, SH, Fairhurst, AM, Mak, A. Clinical utility of circulating anti-N-methyl-d-aspartate receptor subunits NR2A/B antibody for the diagnosis of neuropsychiatric syndromes in systemic lupus erythematosus and Sjogren’s syndrome: an updated meta-analysis. Autoimmunity Rev 2017;16:114–122.Google Scholar
Karaaslan, Z, Ekizoglu, E, Tekturk, P, et al. Investigation of neuronal auto-antibodies in systemic lupus erythematosus patients with epilepsy. Epilepsy Res 2017;129:132–137.Google Scholar
Ludvigsson, JF, Zingone, F, Tomson, T, Ekbom, A, Ciacci, C. Increased risk of epilepsy in biopsy-verified celiac disease: a population-based cohort study. Neurology 2012;78:1401–1407.Google Scholar
Kurien, M, Ludvigsson, JF, Sanders, DS, et al. Persistent mucosal damage and risk of epilepsy in people with celiac disease. Eur J Neurol 2018;25:592-e38.Google Scholar
Gobbi, G. Coeliac disease, epilepsy and cerebral calcifications. Brain Dev 2005;27:189–200.Google Scholar
McKeon, A, Lennon, VA, Pittock, SJ, Kryzer, TJ, Murray, J. The neurologic significance of celiac disease biomarkers. Neurology 2014;83:1789–1796.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] 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
×