AccScience Publishing / AN / Volume 1 / Issue 3 / DOI: 10.36922/an.v1i3.237
Cite this article
Journal Browser
Volume | Year
News and Announcements
View All

Anti-leucine-rich glioma inactivated-1 autoimmune encephalitis: A review of diagnosis and treatment

Ning Gu1† Tian-Yue Meng1† Zhuang Zhu1† Bao-Xin Wu2† Ying-Feng Mu3 De-Qin Geng3*
Show Less
1 School of Clinical Medicine, Xuzhou Medical University, Xuzhou, China
2 Department of Neurology, Peixian People’s Hospital, Xuzhou, China
3 Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Advanced Neurology 2022, 1(3), 237
Submitted: 25 October 2022 | Accepted: 9 December 2022 | Published: 27 December 2022
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Anti-leucine-rich glioma inactivated-1 (LGI1) autoimmune encephalitis is the second most common autoimmune encephalitis, usually with acute or subacute onset. The rates of misdiagnosis and missed diagnosis are high because of its insidious onset. We review the pathogenesis, clinical manifestations, differential diagnosis, treatment, and prognosis of anti-LGI1 autoimmune encephalitis, so as to provide references for clinicians to understand this disease. This disease presents with a variety of clinical manifestations, including faciobrachial dystonic seizure (FBDS), cognitive impairment, hyponatremia, hyperkinetic movements (HMs), and mental impairment. 18F-fluorodeoxyglucose position emission tomography (18F-FDG PET) has higher sensitivity than magnetic resonance imaging (MRI) and can be used to measure disease activity and assess patient response to treatment. The detection of LGI1 antibodies in cerebrospinal fluid or serum is a confirmatory test. The rapid initiation of immunotherapy after diagnosis can significantly improve the prognosis of patients.

Autoimmune encephalitis
Leucine-rich glioma-inactivated-1
Faciobrachial dystonic seizure

Wang JD, Xie L, Fang X, et al., 2022, Clinical validation of the 2020 diagnostic approach for pediatric autoimmune encephalitis in a single center. Zhonghua Er Ke Za Zhi, 60: 786–791.


Baudin P, Cousyn L, Navarro V, et al., 2021, The LGI1 protein: Molecular structure, physiological functions and disruption-related seizures. Cell Mol Life Sci, 79: 16.


Heine J, Pruss H, Kopp UA, et al., 2018, Beyond the limbic system: Disruption and functional compensation of large-scale brain networks in patients with anti-LGI1 encephalitis. J Neurol Neurosurg Psychiatry, 89: 1191–1199.


Herranz-Perez V, Olucha-Bordonau FE, Morante-Redolat JM, et al., 2010, Regional distribution of the leucine-rich glioma inactivated (LGI) gene family transcripts in the adult mouse brain. Brain Res, 1307: 177–194. 


Ohkawa T, Fukata Y, Yamasaki M, et al., 2013, Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors. J Neurosci, 33: 18161–18174.


Fukata Y, Lovero KL, Iwanaga T, et al., 2010, Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. Proc Natl Acad Sci U S A, 107: 3799–3804.


Petit-Pedrol M, Sell J, Planaguma J, et al., 2018, LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain, 141: 3144–3159.


Acsady L, Kamondi A, Sik A, et al., 1998, GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus. J Neurosci, 18: 3386–3403. 


Kalachikov S, Evgrafov O, Ross B, et al., 2002, Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nat Genet, 30: 335–341.


Morante-Redolat JM, Gorostidi-Pagola A, Piquer-Sirerol S, et al., 2002, Mutations in the LGI1/epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy. Hum Mol Genet, 11: 1119–1128.


Yuko F, Xiumin C, Satomi C, et al., 2021, LGI1-ADAM22- MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention. Proc Natl Acad Sci U S A, 118: e2022580118.


Fels E, Muniz-Castrillo S, Vogrig A, et al., 2021, Role of LGI1 protein in synaptic transmission: From physiology to pathology. Neurobiol Dis, 160: 105537.


Guan D, Lee JC, Tkatch T, et al., 2006, Expression and biophysical properties of Kv1 channels in supragranular neocortical pyramidal neurones. J Physiol, 571(Pt 2): 371–389.


Henley JM, Nair JD, Seager R, et al., 2021, Kainate and AMPA receptors in epilepsy: Cell biology, signalling pathways and possible crosstalk. Neuropharmacology, 195: 108569.


Boillot M, Lee CY, Allene C, et al., 2016, LGI1 acts presynaptically to regulate excitatory synaptic transmission during early postnatal development. Sci Rep, 6: 21769.


Zhou YD, Lee S, Jin Z, et al., 2009, Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy. Nat Med, 15: 1208–1214.


Fukata Y, Adesnik H, Iwanaga T, et al., 2006, Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science, 313: 1792–1795.


Lancaster E, Burnor E, Zhang J, et al., 2019, ADAM23 is a negative regulator of Kv1.1/Kv1.4 potassium currents. Neurosci Lett, 704: 159–163.


Ramberger M, Berretta A, Tan JM, et al., 2020, Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms. Brain, 143: 1731–1745. 


Muniz-Castrillo S, Vogrig A, Honnorat J, et al., 2020, Associations between HLA and autoimmune neurological diseases with autoantibodies. Auto Immun Highlights, 11: 2.


Hu F, Liu X, Zhang L, et al., 2020, Novel findings of HLA association with anti-LGI1 encephalitis: HLA-DRB1*03:01 and HLA-DQB1*02:01. J Neuroimmunol, 344: 577243.


Binks S, Varley J, Lee W, et al., 2018, Distinct HLA associations of LGI1 and CASPR2-antibody diseases. Brain, 141: 2263–2271.


Mueller SH, Farber A, Pruss H, et al., 2018, Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis. Ann Neurol, 83: 863–869.


Kim TJ, Lee ST, Moon J, et al., 2017, Anti-LGI1 encephalitis is associated with unique HLA subtypes. Ann Neurol, 81: 183–192.


Van Sonderen A, Roelen DL, Stoop JA, et al., 2017, Anti- LGI1 encephalitis is strongly associated with HLA-DR7 and HLA-DRB4. Ann Neurol, 81: 193–198.


Ding C, Sun Q, Li R, et al., 2022, The first case of familiar anti-leucine-rich glioma-inactivated 1 autoimmune encephalitis: A case report and literature review. Front Neurol, 13: 855383. 


Muniz-Castrillo S, Haesebaert J, Thomas L, et al., 2021, Clinical and prognostic value of immunogenetic characteristics in anti-LGI1 encephalitis. Neurol Neuroimmunol Neuroinflamm, 8: e974.


Taneja V, 2018, Sex hormones determine immune response. Front Immunol, 9: 1931.


Asioli GM, Muccioli L, Barone V, et al., 2022, Anti-LGI1 encephalitis following COVID-19 vaccination: A case series. J Neurol, 269: 5720–5723. 


Zlotnik Y, Gadoth A, Abu-Salameh I, et al., 2021, Case report: Anti-LGI1 encephalitis following COVID-19 vaccination. Front Immunol, 12: 813487.


Thompson J, Bi M, Murchison AG, et al., 2018, The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain, 141: 348–356.


Van Sonderen A, Thijs RD, Coenders EC, et al., 2016, Anti-LGI1 encephalitis: Clinical syndrome and long-term follow-up. Neurology, 87: 1449–1456.


Simabukuro MM, Nobrega PR, Pitombeira M, et al., 2016, The importance of recognizing faciobrachial dystonic seizures in rapidly progressive dementias. Dement Neuropsychol, 10: 351–357.


Gastaldi M, Thouin A, Vincent A, et al., 2016, Antibody-mediated autoimmune encephalopathies and immunotherapies. Neurotherapeutics, 13: 147–162.


Navarro V, Kas A, Apartis E, et al., 2016, Motor cortex and hippocampus are the two main cortical targets in LGI1- antibody encephalitis. Brain, 139(Pt 4): 1079–1093.


Irani SR, Buckley C, Vincent A, et al., 2008, Immunotherapy-responsive seizure-like episodes with potassium channel antibodies. Neurology, 71: 1647–1648.


Irani SR, Michell AW, Lang B, et al., 2011, Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol, 69: 892–900.


Irani SR, Stagg CJ, Schott JM, et al., 2013, Faciobrachial dystonic seizures: The influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain, 136(Pt 10): 3151–3162.


Flanagan EP, Kotsenas AL, Britton JW, et al., 2015, Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures. Neurol Neuroimmunol Neuroinflamm, 2: e161.


Striano P, 2011, Faciobrachial dystonic attacks: Seizures or movement disorder? Ann Neurol, 70: 179–180; author reply 180.


Barajas RF, Collins DE, Cha S, et al., 2010, Adult-onset drug-refractory seizure disorder associated with anti-voltage-gated potassium-channel antibody. Epilepsia, 51: 473–477. 


Liu X, Shan W, Zhao X, et al., 2020, The clinical value of (18) F-FDG-PET in autoimmune encephalitis associated with LGI1 antibody. Front Neurol, 11: 418.


Liu X, Han Y, Yang L, et al., 2020, The exploration of the spectrum of motor manifestations of anti-LGI1 encephalitis beyond FBDS. Seizure, 76: 22–27.


Teng Y, Li T, Yang Z, et al., 2021, Clinical features and therapeutic effects of anti-leucine-rich glioma inactivated 1 encephalitis: A systematic review. Front Neurol, 12: 791014.


Fauser S, Talazko J, Wagner K, et al., 2005, FDG-PET and MRI in potassium channel antibody-associated non-paraneoplastic limbic encephalitis: Correlation with clinical course and neuropsychology. Acta Neurol Scand, 111: 338–343.


Lv RJ, Sun ZR, Cui T, et al., 2014, Temporal lobe epilepsy with amygdala enlargement: A subtype of temporal lobe epilepsy. BMC Neurol, 14: 194. 


Miller TD, Chong TT, Davies AM, et al., 2017, Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis. Brain, 140: 1212–1219.


Szots M, Blaabjerg M, Orsi G, et al., 2017, Global brain atrophy and metabolic dysfunction in LGI1 encephalitis: A prospective multimodal MRI study. J Neurol Sci, 376: 159–165. 


Finke C, Pruss H, Heine J, et al., 2017, Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. JAMA Neurol, 74: 50–59.


Bien CG, Elger CE, 2007, Limbic encephalitis: A cause of temporal lobe epilepsy with onset in adult life. Epilepsy Behav, 10: 529–538.


Lai M, Huijbers MG, Lancaster E, et al., 2010, Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: A case series. Lancet Neurol, 9(8): 776–785.


Tofaris GK, Irani SR, Cheeran BJ, et al., 2012, Immunotherapy-responsive chorea as the presenting feature of LGI1-antibody encephalitis. Neurology, 79: 195–196.


Balint B, Vincent A, Meinck HM, et al., 2018, Movement disorders with neuronal antibodies: Syndromic approach, genetic parallels and pathophysiology. Brain, 141: 13–36.


Gadoth A, Pittock SJ, Dubey D, et al., 2017, Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients. Ann Neurol, 82: 79–92. 


Jang Y, Lee ST, Lim JA, et al., 2018, Psychiatric symptoms delay the diagnosis of anti-LGI1 encephalitis. J Neuroimmunol, 317: 08–14.


Peter-Derex L, Devic P, Rogemond V, et al., 2012, Full recovery of agrypnia associated with anti-Lgi1 antibodies encephalitis under immunomodulatory treatment: A case report with sequential polysomnographic assessment. Sleep Med, 13: 554–556.


Jarius S, Hoffmann L, Clover L, et al., 2008, CSF findings in patients with voltage gated potassium channel antibody associated limbic encephalitis. J Neurol Sci, 268: 74–77.


Li Y, Song F, Liu W, et al., 2021, Clinical features of nine cases of leucine-rich glioma inactivated 1 protein antibody-associated encephalitis. Acta Neurol Belg, 121: 889–897.


Wang M, Cao X, Liu Q, et al., 2017, Clinical features of limbic encephalitis with LGI1 antibody. Neuropsychiatr Dis Treat, 13: 1589–1596. 


Rissanen E, Carter K, Cicero S, et al., 2022, Cortical and subcortical dysmetabolism are dynamic markers of clinical disability and course in anti-LGI1 encephalitis. Neurol Neuroimmunol Neuroinflamm, 9: e1136.


Tripathi M, Tripathi M, Roy SG, et al., 2018, Metabolic topography of autoimmune non-paraneoplastic encephalitis. Neuroradiology, 60: 189–198.


Morano A, Fanella M, Irelli EC, et al., 2020, Seizures in autoimmune encephalitis: Findings from an EEG pooled analysis. Seizure, 83: 160–168. 


Baumgartner T, Pitsch J, Olaciregui-Dague K, et al., 2022, Seizure underreporting in LGI1 and CASPR2 antibody encephalitis. Epilepsia, 63: e100–e105.


Zhong R, Chen Q, Zhang X, et al., 2022, Relapses of anti- NMDAR, anti-GABABR and anti-LGI1 encephalitis: A retrospective cohort study. Front Immunol, 13: 918396.


Irani SR, Pettingill P, Kleopa KA, et al., 2012, Morvan syndrome: Clinical and serological observations in 29 cases. Ann Neurol, 72: 241–255. 


Irani SR, Alexander S, Waters P, et al., 2010, 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, 133: 2734–2748.


Titulaer MJ, Soffietti R, Dalmau J, et al., 2011, Screening for tumours in paraneoplastic syndromes: Report of an EFNS task force. Eur J Neurol, 18: 19–e3.


Maki Y, Takashima H, 2016, Clinical features and treatment of hashimoto encephalopathy. Brain Nerve, 68: 1025–1033.


Huang X., Fan C, Gao L, et al., 2022, Clinical features, immunotherapy, and outcomes of anti-leucine-rich glioma-inactivated-1 encephalitis. J Neuropsychiatry Clin Neurosci, 34: 141–148.


Galeotti C, Kaveri SV, Bayry J, et al., 2017, IVIG-mediated effector functions in autoimmune and inflammatory diseases. Int Immunol, 29: 491–498.


Rodriguez A, Klein CJ, Sechi E, et al., 2022, LGI1 antibody encephalitis: Acute treatment comparisons and outcome. J Neurol Neurosurg Psychiatry, 93: 309–315.


Zhang Y, Huang HJ, Chen WB, et al., 2021, Clinical efficacy of plasma exchange in patients with autoimmune encephalitis. Ann Clin Transl Neurol, 8: 763–773.


Ghimire P, Khanal UP, Gajurel BP, et al., 2020, Anti-LGI1, anti-GABABR, and anti-CASPR2 encephalitides in Asia: A systematic review. Brain Behav, 10: e01793. 


Nepal G, Shing YK, Yadav JK, et al., 2020, Efficacy and safety of rituximab in autoimmune encephalitis: A meta-analysis. Acta Neurol Scand, 142: 449–459. 


Lee WJ, Lee ST, Moon J, et al., 2016, Tocilizumab in autoimmune encephalitis refractory to rituximab: An institutional cohort study. Neurotherapeutics, 13: 824–832. 


De Bruijn MA, van Sonderen A, van Coevorden-Hameete MH, et al., 2019, Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABA(B)R encephalitis. Neurology, 92: e2185–e2196.


Guo K, Liu X, Lin J, et al., 2022, Clinical characteristics, long-term functional outcomes and relapse of anti-LGI1/ Caspr2 encephalitis: A prospective cohort study in Western China. Ther Adv Neurol Disord, 15.


Arino H, Armangue T, Petit-Pedrol M, et al., 2016, Anti- LGI1-associated cognitive impairment: Presentation and long-term outcome. Neurology, 87: 759–765.


Bien CG, Urbach H, Schramm J, et al., 2007, Limbic encephalitis as a precipitating event in adult-onset temporal lobe epilepsy. Neurology, 69: 1236–1244.


Bien CG, Vincent A, Barnett MH, et al., 2012, Immunopathology of autoantibody-associated encephalitides: Clues for pathogenesis. Brain, 135(Pt 5): 1622–1638.

Conflict of interest
The authors report no conflict of interest.
Back to top
Advanced Neurology, Electronic ISSN: 2810-9619 Published by AccScience Publishing