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Leucine-rich glioma-inactivated protein 1 antibody-mediated autoimmune encephalitis in a 4-year-old girl: a case report

Leucine-rich glioma-inactivated protein 1 antibody-mediated autoimmune encephalitis in a... Background: Leucine-rich glioma-inactivated protein 1 (LGI1) antibody-mediated encephalitis is a rare subtype of autoimmune encephalopathy, which is associated with autoimmunity against the neuronal plasma membrane proteins. The characteristic symptoms of this disease are memory dysfunction, seizures, faciobrachial dystonic seizures, cognitive deficits, neuropsychiatric disturbances, and intractable hyponatremia. The diagnosis of this disease mainly depends on the presence of anti-LGI1 antibody in serum or cerebrospinal fluid of patients. LGI1 antibody encephalitis has been reported mostly in adults, with rare occurrences in children. Case presentation: In this report, we described a 4-year-old girl with typical seizures. Seizure types included focal seizures and generalized tonic-clonic seizures. The electroencephalogram findings showed focal discharges. Brain magnetic resonance imaging (MRI) showed normal. The cerebrospinal fluid (CSF) levels of cells, glucose, and chloride were within the normal range, and the culture did not reveal growth of any pathogen. Test of serum LGI1- Ab was positive, while the tests for autoimmune encephalitis antibody series in CSF were negative. The seizures of the patient were completely controlled after the therapy of immunoglobulin, methylprednisolone and antiepileptic drugs (AEDs), and the mental state almost returned to normal. Conclusion: To our knowledge, the patient described here may be the youngest case of LGI1 antibody encephalitis reported to date. Children with the LGI1 antibody-associated encephalitis may present only with single symptoms such as epileptic seizures and have good response to the therapy of immunoglobulin, methylprednisolone and antiepileptic drugs. Our case report will provide hints for pediatricians in the diagnosis and treatment of LGI1- antibody encephalitis. Keywords: Autoimmune encephalitis, LGI1 antibody, Seizures, Electroencephalogram * Correspondence: gaozaifen@163.com Junxia Luo and Jianguo Shi contributed equally to this work. Neurology Department, Qilu Children’s Hospital of Shandong University, Jinan, China Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Luo et al. Acta Epileptologica (2021) 3:4 Page 2 of 6 Background The patient was treated with intravenous immuno- The leucine-rich glioma inactivated 1 (LGI1) antibody- globulin (1 g/kg per day for 4 days) (divided into two mediated encephalitis is a subtype of autoimmune en- doses) and methylprednisolone pulse therapy (50 mg/ cephalopathy, which is associated with the generation of kg per day for 3 consecutive days; 3 times total with antibodies against the neuronal plasma membrane pro- intervals of 4 days; total course lasting 21 days), in teins [1]. The characteristic symptoms of this disease combination with antiepileptic drugs (AEDs) (leveti- include memory dysfunction, seizures, faciobrachial dys- racetam 0.2 g bid, clonazepam 0.25 mg bid, and oxcar- tonic seizures (FBDS), cognitive deficits, neuropsychi- bazepine 0.15 g bid). The patient had good response atric disturbances, and intractable hyponatremia [2]. The to immunotherapy, with no recurrence of seizure after diagnosis of LGI1 antibody-mediated encephalitis is the first stage of immunotherapy. Simultaneously, her based on the presence of LGI1 antibody in the serum or panicattackssubsided. Theprednisolone(15mg;daily cerebrospinal fluid (CSF). LGI1-antibody encephalitis oral) therapy was administered subsequently. The dos- has been reported predominantly in adults, yet rarely in age was gradually reduced throughout the treatment children. for 3 months. At 15 days after discharge, the VEEG In this report, we describe a 4-year-old Chinese girl examination was performed again and had normal re- with LGI1-antibody encephalitis who experienced fever sults, except the presence of mild sharp waves in the over the course of 10 days and suffered multiple episodes left forehead (Fig. 4). During the 60-day follow-up, of seizure, with abnormal electroencephalogram (EEG) seizures did not recur, and the mental state of the pa- findings during the natural course of the disease. To our tient returned to the level before disease onset. best knowledge, this is the youngest case of LGI1- antibody encephalitis reported to date. Discussion According to the Chinese expert consensus on the Case presentation diagnosis and management of autoimmune encephal- The case was a 4-year-old Chinese girl who was admit- itis, the criteria for definite diagnosis of LGI1- ted to our hospital with generalized tonic-clonic sei- antibody encephalitis are as follows: (1) having acute zures. She had an approximately 10-day history of or subacute onset with progressive aggravation; (2) discontinuous fever before the seizure onset. At the be- presenting with clinical features of limbic encephalitis ginning of the course, she only experienced generalized or FBDS; (3) having normal leukocyte count or mild tonic-clonic seizures, which lasted about 10 min and lymphocyte reaction on CSF examination; (4) showing were then relieved. After hospitalization, she experienced abnormal brain MRI signals in the bilateral or unilat- frequent panic attacks with hypermotor seizure, while eral medial temporal lobe; (5) showing abnormal EEG the heart rate was normal, and no auro or disturbance of activity; and (6) tested positive for serum and/or CSF consciousness occurred. This condition self-resolved anti-LGIl antibody. The case presented here had an within a few minutes but occurred with a frequency of acute onset of the disease and experienced frequent dozens of times a day. No apparent positive signs were panic attacks, which is a clinical feature of limbic en- identified on a nervous system examination; however, cephalitis. These symptoms, combined with the ab- she showed mild dysphoria, irritability, insomnia and de- normal EEG findings and positive anti-LGIl antibody creased level of consciousness. Video electroencephalo- in the serum and CSF, supported the diagnosis of gram (VEEG; Fig. 1) revealed continuous epileptiform LGI1-antibody encephalitis. discharges in the left anterior region. In addition, two The LGI1-antibody encephalitis occurs predomin- focal seizure onsets from the left anterior region were antly in males, with a mean onset age of ~ 60 years detected. Tumor marker and paraneoplastic neuronal (typical range, 30–80 years) [3]. Pediatric cases have antibody (anti-Hu, anti-Ri, anti-Yo, anti-Ma2/Ta, anti- been rarely reported [4]. Schimmel reported in 2017 a CV2, and anti-Amphiphysin) tests were negative. The 14-year-old boy who was diagnosed with the LGI1- CSF levels of cells, glucose, and chloride were within the antibody encephalitis [5], and Zhang et al. reported an 8- normal range, and CSF culture did not reveal growth of year-old Chinese boy with the symptom of reduced any pathogen. Test of serum LGI1-Ab was positive (titer, night-time sleep in 2018 [6]. Therefore, to our best know- 1:30; Fig. 2), whereas the test for CSF LGI1-Ab was ledge, the patient reported here is the youngest case re- negative. Moreover, the tests for autoimmune encephal- ported to date. itis antibody series in CSF were negative. Brain magnetic Autoimmune encephalitis is a type of inflammation in resonance imaging (MRI) did not reveal abnormalities the central nervous system. Studies have reported that (Fig. 3). Serum sodium levels were within the normal the LGI1-antibody encephalitis is the second most com- range throughout the disease course. Abdomen ultra- mon form of autoimmune encephalitis [7]. There is a sound and chest radiography showed no signs of tumor. high incidence of epileptic seizures during the acute Luo et al. Acta Epileptologica (2021) 3:4 Page 3 of 6 Fig. 1 Video electroencephalography recordings. a EEG background is normal. Interictal EEG showed left forehead spike waves, sharp waves, and spike (or sharp) slow wave complexes. b Ictal EEG shows rhythmic sharp slow wave complexes in the left anterior head region, followed by low- voltage fast activity and rhythmic spike waves; these were contaminated by movements or muscle artifacts, and evolved to the left hemisphere, with occasional insertion of slow waves. The whole procedure lasted for 1–2 min. Moreover, scared facial expressions, hypermotor seizure were observed clinically (lasting for about 1–2 min). EEG, electroencephalogram phase of autoimmune encephalitis. In this context, the yet be defined as epilepsy. In 2017, the ILAE further pro- seizures may be an acute or induced symptom, and can posed a new classification of epilepsy, the “epilepsy of be considered as autoimmune seizures, which has a immune etiology”, for patients whose epilepsy “results prevalence of 60–100% [8]. According to the 2014 edi- directly from an immune disorder in which seizures are tion of Epilepsy Usability Definition by the International a core symptom of the disorder” [10]. Multiple frequent League Against Epilepsy (ILAE) [9], the acutely pro- seizure semiology and subclinical seizures associated voked or acute symptomatic seizures at this stage cannot with temporal and frontal discharges have been reported Luo et al. Acta Epileptologica (2021) 3:4 Page 4 of 6 in the LGI1-antibody encephalitis patients [11], and in our case the discharges were also concentrated in the frontal lobe. Some cases also showed frequent early sei- zures of encephalitis as clinical manifestations [12]. Con- sistently, the case in our report also displayed seizures as the first symptom. In addition, the symptoms, the presence of antibody, and the treatment response of this case were all similar to those of adult patients. However, our patient did not show FBDS or hyponatremia, which are hallmark symp- toms in adult patients with LGI1-antibody encephalitis [13]. Therefore, the diagnosis of LGI1-antibody enceph- alitis should be considered if pediatric patients display acute and progressing unexplained frequent episodes of Fig. 2 The result of anti-leucine-rich, glioma inactivation-1 antibody. seizures, in order to prevent misdiagnosis and missed A 4-year-old girl with positive serum anti-leucine-rich, glioma diagnosis. In fact, seizures are extraordinarily frequent in inactivation-1 antibody on indirect immunofluorescence test the acute, inflammatory-provoked phase of many types (green fluorescence) of antibody-mediated encephalitis, especially in the LGI1-antibody encephalitis, but in most patients the sei- zures are not sustained and will resolve after the enceph- alitis remission [8]. However, a recent study showed that after 2 years’ follow-up, 14% of patients with LGI1- antibody encephalitis still had seizures and an additional Fig. 3 MRI showed unremarkable findings before (a) and after (b) treatment Luo et al. Acta Epileptologica (2021) 3:4 Page 5 of 6 14% were still on AEDs after the encephalitis was cured [1]. Some scholars have suggested that the epileptiform seizures in the acute phase of autoimmune encephalitis cannot be diagnosed as epilepsy, instead, it should be followed up for at least 1 year to detect the presence of persistent seizures to determine the continued use of AEDs [8]. It is currently believed that the abnormalities in EEG and brain imaging are the most predictive factors for epilepsy after autoimmune encephalitis [14]. In this report, the patient showed normal results of brain im- aging, and her seizures and EEG abnormality were im- proved as her encephalitis was controlled. However, as the follow-up time was not long enough in this report, we would continue to follow up to observe the prognosis of this patient. Conclusion The LGI1-antibody encephalitis is a newly discovered autoimmune disease in recent years, which is character- ized by specific FBDS and hyponatremia and responds well to immunosuppressive therapy. Here we reported a 4-year-old Chinese girl with LGI1-antibody encephalitis, who may be the youngest patient reported in literature. Children with the LGI1 antibody-associated encephalitis may present only with single symptoms such as epileptic seizures while other symptoms of encephalitis may not appear, particularly in younger age groups. This study demonstrates that early diagnosis and treatment have more benefits for seizure control and improvement of mental recovery. The diagnosis of this disease should be confirmed by anti-LGI1-antibody detection, cranial MRI examination, VEEG and other assistant examinations to avoid missed diagnosis. Our case report will provide hints for pediatricians in the diagnosis and treatment of LGI1-antibody encephalitis. Abbreviations LGI1: Leucine-rich, glioma inactivated 1; FBDS: Faciobrachial dystonic seizures; CSF: Cerebrospinal fluid; EEG: Electroencephalogram; VEEG: Video electroencephalogram; MRI: Magnetic resonance imaging; ILAE: International league against epilepsy; AEDs: Antiepileptic drugs Acknowledgements We thank the affected individuals and their families for participating in this report. Authors’ contributions JXL, JGS, YHC, WDH, YJG, GSH and ZFG collected and analyzed clinical data, JXL and JGS wrote the manuscript, together with contributions from all authors. All authors read and approved the final manuscript. Funding The study was not supported by any funding. Availability of data and materials Supporting data are available upon request. Fig. 4 EEG recordings obtained after half a month. a EEG background appears normal. b Interictal EEG shows few spike waves and sharp Ethics approval and consent to participate waves in the sleep stage in the left forehead. EEG, electroencephalogram Not applicable. Luo et al. Acta Epileptologica (2021) 3:4 Page 6 of 6 Consent for publication All authors agreed for the publication of this study. Competing interests The authors have declared that they have no competing interests. Author details Neurology Department, Qilu Children’s Hospital of Shandong University, Jinan, China. Functional Neurosurgery Department, Qilu Children’s Hospital of Shandong University, Jinan, China. Received: 30 August 2020 Accepted: 8 February 2021 References 1. Van Sonderen A, Thijs RD, Coenders EC, Jiskoot LC, Sanchez E, De Bruijn MA, et al. Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology. 2016;87(14):1449–56. 2. Bing-Lei W, Jia-Hua Z, Yan L, Zan Y, Xin B, Jian-Hua S, et al. Three cases of antibody-LGI-1 limbic encephalitis and review of literature. Int J Neurosci. 2019;129(7):642–8. 3. Van Sonderen A, Petit-Pedrol M, Dalmau J, Titulaer MJ. The value of LGI-1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis. Nat Rev Neurol. 2017;13(5):290–301. 4. López-Chiriboga AS, Klein C, Zekeridou A, McKeon A, Dubey D, Flanagan EP, et al. LGI1 and CASPR2 neurological autoimmunity in children. Ann Neurol. 2018;84(3):473–80. 5. Schimmel M, Frühwald MC, Bien CG. Limbic encephalitis with LGI-1 antibodies in a 14-year-old boy. Eur J Paediatr Neurol. 2018;22(1):190–3. 6. Jian-zhao Z, Cui-juan X, Xiu-shan G, Ping Z, Hai-tao R, Xiao-qiu S, et al. Two cases of children with leucine-rich glioma-inactivated 1 protein antibody related encephalitis and literature review. Chin J Obstet Gynecol Pediatr. 2018;14(3):305–10. 7. 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(2):839–87. 8. Geis C, Planagumà J, Carreño M, Graus F, Dalmau J. Autoimmune seizures and epilepsy. J Clin Invest. 2019;129(3):926–40. 9. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014; 55(4):475–82. 10. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512–21. 11. Aurangzeb S, Symmondset M, Knight RK, Kennett R, Wehner T, Irani SR. LGI1-antibody encephalitis is characterised by frequent, multifocal clinical and subclinical seizures. Seizure. 2017;50:14–7. 12. Deng S, Qiu K, Liu H, Wu X, Lei Q, Lu W. Clinical characteristics and short- term prognosis of autoimmune encephalitis: a single-center cohort study in Changsha, China. Front Neurol. 2019;10:539. 13. Irani SR, Michell AW, Lang B, Pettingill P, Waters P, Johnson MR, et al. Facio- brachial dystonic seizures precede LGI-1 antibody limbic encephalitis. Ann Neurol. 2011;69(5):892–900. 14. Navarro V, Kas A, Apartis E, Chami L, Rogemond V, Levy P, et al. Motor cortex and hippocampus are the two main cortical targets in LGI1-antibody encephalitis. Brain. 2016;139(Pt 4):1079–93. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Acta Epileptologica Springer Journals

Leucine-rich glioma-inactivated protein 1 antibody-mediated autoimmune encephalitis in a 4-year-old girl: a case report

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Springer Journals
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Copyright © The Author(s) 2021
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2524-4434
DOI
10.1186/s42494-021-00039-z
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Abstract

Background: Leucine-rich glioma-inactivated protein 1 (LGI1) antibody-mediated encephalitis is a rare subtype of autoimmune encephalopathy, which is associated with autoimmunity against the neuronal plasma membrane proteins. The characteristic symptoms of this disease are memory dysfunction, seizures, faciobrachial dystonic seizures, cognitive deficits, neuropsychiatric disturbances, and intractable hyponatremia. The diagnosis of this disease mainly depends on the presence of anti-LGI1 antibody in serum or cerebrospinal fluid of patients. LGI1 antibody encephalitis has been reported mostly in adults, with rare occurrences in children. Case presentation: In this report, we described a 4-year-old girl with typical seizures. Seizure types included focal seizures and generalized tonic-clonic seizures. The electroencephalogram findings showed focal discharges. Brain magnetic resonance imaging (MRI) showed normal. The cerebrospinal fluid (CSF) levels of cells, glucose, and chloride were within the normal range, and the culture did not reveal growth of any pathogen. Test of serum LGI1- Ab was positive, while the tests for autoimmune encephalitis antibody series in CSF were negative. The seizures of the patient were completely controlled after the therapy of immunoglobulin, methylprednisolone and antiepileptic drugs (AEDs), and the mental state almost returned to normal. Conclusion: To our knowledge, the patient described here may be the youngest case of LGI1 antibody encephalitis reported to date. Children with the LGI1 antibody-associated encephalitis may present only with single symptoms such as epileptic seizures and have good response to the therapy of immunoglobulin, methylprednisolone and antiepileptic drugs. Our case report will provide hints for pediatricians in the diagnosis and treatment of LGI1- antibody encephalitis. Keywords: Autoimmune encephalitis, LGI1 antibody, Seizures, Electroencephalogram * Correspondence: gaozaifen@163.com Junxia Luo and Jianguo Shi contributed equally to this work. Neurology Department, Qilu Children’s Hospital of Shandong University, Jinan, China Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Luo et al. Acta Epileptologica (2021) 3:4 Page 2 of 6 Background The patient was treated with intravenous immuno- The leucine-rich glioma inactivated 1 (LGI1) antibody- globulin (1 g/kg per day for 4 days) (divided into two mediated encephalitis is a subtype of autoimmune en- doses) and methylprednisolone pulse therapy (50 mg/ cephalopathy, which is associated with the generation of kg per day for 3 consecutive days; 3 times total with antibodies against the neuronal plasma membrane pro- intervals of 4 days; total course lasting 21 days), in teins [1]. The characteristic symptoms of this disease combination with antiepileptic drugs (AEDs) (leveti- include memory dysfunction, seizures, faciobrachial dys- racetam 0.2 g bid, clonazepam 0.25 mg bid, and oxcar- tonic seizures (FBDS), cognitive deficits, neuropsychi- bazepine 0.15 g bid). The patient had good response atric disturbances, and intractable hyponatremia [2]. The to immunotherapy, with no recurrence of seizure after diagnosis of LGI1 antibody-mediated encephalitis is the first stage of immunotherapy. Simultaneously, her based on the presence of LGI1 antibody in the serum or panicattackssubsided. Theprednisolone(15mg;daily cerebrospinal fluid (CSF). LGI1-antibody encephalitis oral) therapy was administered subsequently. The dos- has been reported predominantly in adults, yet rarely in age was gradually reduced throughout the treatment children. for 3 months. At 15 days after discharge, the VEEG In this report, we describe a 4-year-old Chinese girl examination was performed again and had normal re- with LGI1-antibody encephalitis who experienced fever sults, except the presence of mild sharp waves in the over the course of 10 days and suffered multiple episodes left forehead (Fig. 4). During the 60-day follow-up, of seizure, with abnormal electroencephalogram (EEG) seizures did not recur, and the mental state of the pa- findings during the natural course of the disease. To our tient returned to the level before disease onset. best knowledge, this is the youngest case of LGI1- antibody encephalitis reported to date. Discussion According to the Chinese expert consensus on the Case presentation diagnosis and management of autoimmune encephal- The case was a 4-year-old Chinese girl who was admit- itis, the criteria for definite diagnosis of LGI1- ted to our hospital with generalized tonic-clonic sei- antibody encephalitis are as follows: (1) having acute zures. She had an approximately 10-day history of or subacute onset with progressive aggravation; (2) discontinuous fever before the seizure onset. At the be- presenting with clinical features of limbic encephalitis ginning of the course, she only experienced generalized or FBDS; (3) having normal leukocyte count or mild tonic-clonic seizures, which lasted about 10 min and lymphocyte reaction on CSF examination; (4) showing were then relieved. After hospitalization, she experienced abnormal brain MRI signals in the bilateral or unilat- frequent panic attacks with hypermotor seizure, while eral medial temporal lobe; (5) showing abnormal EEG the heart rate was normal, and no auro or disturbance of activity; and (6) tested positive for serum and/or CSF consciousness occurred. This condition self-resolved anti-LGIl antibody. The case presented here had an within a few minutes but occurred with a frequency of acute onset of the disease and experienced frequent dozens of times a day. No apparent positive signs were panic attacks, which is a clinical feature of limbic en- identified on a nervous system examination; however, cephalitis. These symptoms, combined with the ab- she showed mild dysphoria, irritability, insomnia and de- normal EEG findings and positive anti-LGIl antibody creased level of consciousness. Video electroencephalo- in the serum and CSF, supported the diagnosis of gram (VEEG; Fig. 1) revealed continuous epileptiform LGI1-antibody encephalitis. discharges in the left anterior region. In addition, two The LGI1-antibody encephalitis occurs predomin- focal seizure onsets from the left anterior region were antly in males, with a mean onset age of ~ 60 years detected. Tumor marker and paraneoplastic neuronal (typical range, 30–80 years) [3]. Pediatric cases have antibody (anti-Hu, anti-Ri, anti-Yo, anti-Ma2/Ta, anti- been rarely reported [4]. Schimmel reported in 2017 a CV2, and anti-Amphiphysin) tests were negative. The 14-year-old boy who was diagnosed with the LGI1- CSF levels of cells, glucose, and chloride were within the antibody encephalitis [5], and Zhang et al. reported an 8- normal range, and CSF culture did not reveal growth of year-old Chinese boy with the symptom of reduced any pathogen. Test of serum LGI1-Ab was positive (titer, night-time sleep in 2018 [6]. Therefore, to our best know- 1:30; Fig. 2), whereas the test for CSF LGI1-Ab was ledge, the patient reported here is the youngest case re- negative. Moreover, the tests for autoimmune encephal- ported to date. itis antibody series in CSF were negative. Brain magnetic Autoimmune encephalitis is a type of inflammation in resonance imaging (MRI) did not reveal abnormalities the central nervous system. Studies have reported that (Fig. 3). Serum sodium levels were within the normal the LGI1-antibody encephalitis is the second most com- range throughout the disease course. Abdomen ultra- mon form of autoimmune encephalitis [7]. There is a sound and chest radiography showed no signs of tumor. high incidence of epileptic seizures during the acute Luo et al. Acta Epileptologica (2021) 3:4 Page 3 of 6 Fig. 1 Video electroencephalography recordings. a EEG background is normal. Interictal EEG showed left forehead spike waves, sharp waves, and spike (or sharp) slow wave complexes. b Ictal EEG shows rhythmic sharp slow wave complexes in the left anterior head region, followed by low- voltage fast activity and rhythmic spike waves; these were contaminated by movements or muscle artifacts, and evolved to the left hemisphere, with occasional insertion of slow waves. The whole procedure lasted for 1–2 min. Moreover, scared facial expressions, hypermotor seizure were observed clinically (lasting for about 1–2 min). EEG, electroencephalogram phase of autoimmune encephalitis. In this context, the yet be defined as epilepsy. In 2017, the ILAE further pro- seizures may be an acute or induced symptom, and can posed a new classification of epilepsy, the “epilepsy of be considered as autoimmune seizures, which has a immune etiology”, for patients whose epilepsy “results prevalence of 60–100% [8]. According to the 2014 edi- directly from an immune disorder in which seizures are tion of Epilepsy Usability Definition by the International a core symptom of the disorder” [10]. Multiple frequent League Against Epilepsy (ILAE) [9], the acutely pro- seizure semiology and subclinical seizures associated voked or acute symptomatic seizures at this stage cannot with temporal and frontal discharges have been reported Luo et al. Acta Epileptologica (2021) 3:4 Page 4 of 6 in the LGI1-antibody encephalitis patients [11], and in our case the discharges were also concentrated in the frontal lobe. Some cases also showed frequent early sei- zures of encephalitis as clinical manifestations [12]. Con- sistently, the case in our report also displayed seizures as the first symptom. In addition, the symptoms, the presence of antibody, and the treatment response of this case were all similar to those of adult patients. However, our patient did not show FBDS or hyponatremia, which are hallmark symp- toms in adult patients with LGI1-antibody encephalitis [13]. Therefore, the diagnosis of LGI1-antibody enceph- alitis should be considered if pediatric patients display acute and progressing unexplained frequent episodes of Fig. 2 The result of anti-leucine-rich, glioma inactivation-1 antibody. seizures, in order to prevent misdiagnosis and missed A 4-year-old girl with positive serum anti-leucine-rich, glioma diagnosis. In fact, seizures are extraordinarily frequent in inactivation-1 antibody on indirect immunofluorescence test the acute, inflammatory-provoked phase of many types (green fluorescence) of antibody-mediated encephalitis, especially in the LGI1-antibody encephalitis, but in most patients the sei- zures are not sustained and will resolve after the enceph- alitis remission [8]. However, a recent study showed that after 2 years’ follow-up, 14% of patients with LGI1- antibody encephalitis still had seizures and an additional Fig. 3 MRI showed unremarkable findings before (a) and after (b) treatment Luo et al. Acta Epileptologica (2021) 3:4 Page 5 of 6 14% were still on AEDs after the encephalitis was cured [1]. Some scholars have suggested that the epileptiform seizures in the acute phase of autoimmune encephalitis cannot be diagnosed as epilepsy, instead, it should be followed up for at least 1 year to detect the presence of persistent seizures to determine the continued use of AEDs [8]. It is currently believed that the abnormalities in EEG and brain imaging are the most predictive factors for epilepsy after autoimmune encephalitis [14]. In this report, the patient showed normal results of brain im- aging, and her seizures and EEG abnormality were im- proved as her encephalitis was controlled. However, as the follow-up time was not long enough in this report, we would continue to follow up to observe the prognosis of this patient. Conclusion The LGI1-antibody encephalitis is a newly discovered autoimmune disease in recent years, which is character- ized by specific FBDS and hyponatremia and responds well to immunosuppressive therapy. Here we reported a 4-year-old Chinese girl with LGI1-antibody encephalitis, who may be the youngest patient reported in literature. Children with the LGI1 antibody-associated encephalitis may present only with single symptoms such as epileptic seizures while other symptoms of encephalitis may not appear, particularly in younger age groups. This study demonstrates that early diagnosis and treatment have more benefits for seizure control and improvement of mental recovery. The diagnosis of this disease should be confirmed by anti-LGI1-antibody detection, cranial MRI examination, VEEG and other assistant examinations to avoid missed diagnosis. Our case report will provide hints for pediatricians in the diagnosis and treatment of LGI1-antibody encephalitis. Abbreviations LGI1: Leucine-rich, glioma inactivated 1; FBDS: Faciobrachial dystonic seizures; CSF: Cerebrospinal fluid; EEG: Electroencephalogram; VEEG: Video electroencephalogram; MRI: Magnetic resonance imaging; ILAE: International league against epilepsy; AEDs: Antiepileptic drugs Acknowledgements We thank the affected individuals and their families for participating in this report. Authors’ contributions JXL, JGS, YHC, WDH, YJG, GSH and ZFG collected and analyzed clinical data, JXL and JGS wrote the manuscript, together with contributions from all authors. All authors read and approved the final manuscript. Funding The study was not supported by any funding. Availability of data and materials Supporting data are available upon request. Fig. 4 EEG recordings obtained after half a month. a EEG background appears normal. b Interictal EEG shows few spike waves and sharp Ethics approval and consent to participate waves in the sleep stage in the left forehead. EEG, electroencephalogram Not applicable. Luo et al. Acta Epileptologica (2021) 3:4 Page 6 of 6 Consent for publication All authors agreed for the publication of this study. Competing interests The authors have declared that they have no competing interests. Author details Neurology Department, Qilu Children’s Hospital of Shandong University, Jinan, China. Functional Neurosurgery Department, Qilu Children’s Hospital of Shandong University, Jinan, China. Received: 30 August 2020 Accepted: 8 February 2021 References 1. Van Sonderen A, Thijs RD, Coenders EC, Jiskoot LC, Sanchez E, De Bruijn MA, et al. Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology. 2016;87(14):1449–56. 2. Bing-Lei W, Jia-Hua Z, Yan L, Zan Y, Xin B, Jian-Hua S, et al. Three cases of antibody-LGI-1 limbic encephalitis and review of literature. Int J Neurosci. 2019;129(7):642–8. 3. Van Sonderen A, Petit-Pedrol M, Dalmau J, Titulaer MJ. The value of LGI-1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis. Nat Rev Neurol. 2017;13(5):290–301. 4. López-Chiriboga AS, Klein C, Zekeridou A, McKeon A, Dubey D, Flanagan EP, et al. LGI1 and CASPR2 neurological autoimmunity in children. Ann Neurol. 2018;84(3):473–80. 5. Schimmel M, Frühwald MC, Bien CG. Limbic encephalitis with LGI-1 antibodies in a 14-year-old boy. Eur J Paediatr Neurol. 2018;22(1):190–3. 6. Jian-zhao Z, Cui-juan X, Xiu-shan G, Ping Z, Hai-tao R, Xiao-qiu S, et al. Two cases of children with leucine-rich glioma-inactivated 1 protein antibody related encephalitis and literature review. Chin J Obstet Gynecol Pediatr. 2018;14(3):305–10. 7. Dalmau J, Geis C, Graus F. 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Published: Feb 27, 2021

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