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Background and Purpose: This study was undertaken to investigate the association between human leukocyte antigen (HLA) genotype and clinical characteristics of anti-LGI1 encephalitis., Methods: HLA genotyping was performed in 34 patients with anti-LGI1 encephalitis admitted to West China Hospital between April 2014 and May 2021, as well as in 305 healthy controls. The online tool NetMHCIIpan 4.0 and AutoDock Vina software were used to predict binding between LGI1 peptide and HLA class II molecules., Results: Risk of anti-LGI1 encephalitis was strongly associated with the DRB1*03:01 allele (odds ratio [OR] = 4.31, 95% confidence interval [CI] = 1.96-9.25, corrected p = 2.75 × 10 -4 ) and the DRB1*03:01-DQB1*02:01 haplotype (OR = 4.45, 95% CI = 2.02-9.59, corrected p = 2.94 × 10 -4 ). Compared to carriers of the DRB1*07:01 allele, those with the DRB1*03:01 allele were more likely to be female (93.3% vs. 33.3%, p = 0.004) and to be younger (median age = 38 vs. 65 years, p < 0.001). DRB1*03:01 carriers showed stronger response to immunotherapy than carriers of the DRB1*07:01 allele, based on median score decrease on the modified Rankin scale (2, interquartile range = 1-2 vs. 1, interquartile range = 0-1; p = 0.03) at 4 weeks after immunotherapy. Prediction and docking algorithms suggested that the LGI1 peptide can bind to the DRB1*03:01 molecule strongly., Conclusions: The strong association between anti-LGI1 encephalitis and certain HLA class II alleles supports a primary autoimmune origin for the disease. Carriers of the DRB1*03:01 allele in Chinese patients with anti-LGI1 encephalitis are more likely to be female, to suffer earlier disease onset, and to respond better to immunotherapy., (© 2022 European Academy of Neurology.)

Objective: The investigators aimed to explore the clinical characteristics, immunotherapy, and outcomes of patients with antileucine-rich glioma-inactivated-1 (anti-LGI1) encephalitis., Methods: Data on participants' clinical characteristics, laboratory findings, radiological and electroencephalogram (EEG) features, treatment, and outcomes from January 2012 to December 2016 were collected. Statistical analysis was conducted to assess the factors associated with patient functional outcome. Forty-three patients were enrolled in the study, with a predominance of males (65.1%). The median age at onset was 57 years (interquartile range [IQR]: 44.0-65.0). The median time from onset to diagnosis was 60 days (IQR: 37.0-127.0)., Results: The main clinical manifestations included epilepsy (100%), faciobrachial dystonic seizures (FBDS; 44.2%), cognitive dysfunction (95.3%), neuropsychiatric disturbances (76.7%), sleep disorders (58.1%), and disturbance of consciousness (48.8%). Twenty-two patients (51.2%) had hyponatremia, 31 (72.1%) had abnormal EEG results, and 30 (69.8%) had abnormal brain MRI scans, mainly involving the hippocampus (76.7%) or temporal lobe (40%). Twenty of 34 patients (58.8%) in a follow-up MRI examination exhibited hippocampal atrophy. Twenty-five patients (58.2%) were administered corticosteroids and intravenous immunoglobulin, whereas 17 patients were treated only with corticosteroids. Forty-one patients (95.3%) had favorable outcomes after a median of 21.5 months (IQR: 7-43) of follow-up. Serum sodium level was a factor associated with a disabled status (odds ratio=0.81, 95% CI=0.66, 0.98, p=0.03). Anti-LGI1 encephalitis patients were characterized by seizures, FBDS, cognitive deficits, neuropsychiatric disturbances, and hyponatremia., Conclusions: Most patients with anti-LGI1 encephalitis are nonparaneoplastic, have low recurrence rates, and have favorable prognostic outcomes. Rapid evaluation, prompt immunotherapy, and long-term follow-up are essential in the care of anti-LGI1 encephalitis patients.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is infrequently reported but more and more recognizable in children. Here we give detailed description of the clinical features and long-term outcome of three cases of childhood onset anti-LGI1 encephalitis. Methods: Three anti-LGI1 encephalitis patients were hospitalized in the Department of Pediatrics at Qilu Hospital of Shandong University. Data about the clinical manifestations, treatments and long-term follow-up outcomes were described in detail. Results: Case 1 showed an adolescent girl with initiating symptom of acuteonset frequent focal seizures. Her serum LGI1-antibody test was positive, and she had a good response to antiseizure medication (ASM) and IVIG. Case 2 showed a preschool-age boy with long-period refractory focal seizures and recent behavioral change. Both serum and cerebrospinal fluid (CSF) tests of LGI1-antibody were positive, and the MRI showed progressive atrophy in the left hemisphere. The symptoms got improved after receiving second-line immunotherapy initially but there are still the sequelae of drug-resistant epilepsy and mild to moderate intellectual disability. Case 3 showed an adolescent boy with initiating symptom of acute-onset frequent focal seizures. Both serum and CSF tests of LGI1-antibody were positive, and he had a good response to immunotherapy. By analyzing all literature-reported 19 pediatric cases, we found pediatric anti-LGI1 encephalitis is more common in female and adolescent. Seizures and behavioral changes were the most common symptoms. CSF pleocytosis and LGI1-antibodies results were mostly negative. Most patients showed good response to immunotherapy. Conclusion: Childhood onset anti-LGI1 encephalitis is a heterogeneous clinical syndrome, ranging from typical limbic encephalitis to isolating focal seizures. It is important to test autoimmune antibodies when encountering similar cases and repeat antibody testing if necessary. Timely recognition leads to earlier diagnosis and more rapid initiation of effective immunotherapy and potentially better outcomes. [ABSTRACT FROM AUTHOR]

BackgroundAnti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a limbic encephalitis that rarely presents as an isolated psychiatric syndrome.Case presentationA 70-year-old patient first presented with behavioral disorder including hyperactivity, euphoria, with disinhibition and accelerated speech associated with severe insomnia and cognitive disorder. A manic episode was diagnosed and he received various psychotropic medications with no improvement. Invesitgations were negative (MRI showed T2 aspecific hyperintensities with no hyperintensities in limbic regions and EEG was normal). He was transferred to a nursing home, with a diagnosis of neurodegenerative condition. Later, he was referred to our unit for further investigations. A cerebral 18F-FDG-PET revealed an association of frontal hypometabolism and temporal and striatum hypermetabolism and CSF analysis revealed slightly increased white blood cell counts. Plasmatic anti-LGI1 antibodies were detected. The patient was treated with intra-venous immunoglobulin (IvIg) but showed no improvement. Second-line treatment (a combination of rituximab and cyclophosmphamide) was then administered for a year, leading to an improvement of neuropsychiatric symptoms and normalization of metabolic impairment on 18F-FDG-PET.ConclusionIn this report, we describe a novel case of a patient withanti-LGI1 encephalitis with a predominant long-term psychiatric presentation. An atypical presentation (such as atypical psychiatric symptoms, neurocognitive disorder, and hyponatremia) should prompt further investigations such as CSF analysis, considering that MRI and EEG may be normal. FDG-PET might be of interest but few data are available in the literature. Early treatment of anti-LGI1 encephalitis is crucial for overall prognosis and may delay the development of dementia in some cases.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is typically characterized by limbic encephalitis, faciobrachial dystonic seizures and hyponatremia. The frequency with which milder forms of anti-LGI1 encephalitis mimic isolated psychiatric syndromes, such as psychoses, or may lead to dementia if untreated, is largely unknown. Case presentation: Here, the authors present a 50-year-old patient who had suffered from neurocognitive deficits and predominant delusions for over one and a half years. He reported a pronounced feeling of thirst, although he was drinking 10–20 liters of water each day, and he was absolutely convinced that he would die of thirst. Due to insomnia in the last five years, the patient took Z-drugs; later, he also abused alcohol. Two years prior to admission, he developed a status epilepticus which had been interpreted as a withdrawal seizure. In his serum, anti-LGI1 antibodies were repeatedly detected by different independent laboratories. Cerebrospinal fluid analyses revealed slightly increased white blood cell counts and evidence for blood–brain-barrier dysfunction. Magnetic resonance imaging showed hyperintensities mesio-temporally and in the right amygdala. In addition, there was a slight grey–white matter blurring. A cerebral [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) examination of his brain showed moderate hypometabolism of the bilateral rostral mesial to medial frontal cortices. Treatment attempts with various psychotropic drugs remained unsuccessful in terms of symptom relief. After the diagnosis of probable chronified anti-LGI1 encephalitis was made, two glucocorticoid pulse treatments were performed, which led to a slight improvement of mood and neurocognitive deficits. Further therapy was not desired by the patient and his legally authorized parents. Conclusion: This case study describes a patient with anti-LGI1 encephalitis in the chronified stage and a predominant long-lasting psychiatric course with atypical symptoms of psychosis and typical neurocognitive deficits. The patient’s poor response to anti-inflammatory drugs was probably due to the delayed start of treatment. This delay in diagnosis and treatment may also have led to the FDG-PET findings, which were compatible with frontotemporal dementia (“state of damage”). In similar future cases, newly occurring epileptic seizures associated with psychiatric symptoms should trigger investigations for possible autoimmune encephalitis, even in patients with addiction or other pre-existing psychiatric conditions. This should in turn result in rapid organic clarification and—in positive cases—to anti-inflammatory treatment. Early treatment of anti-LGI1 encephalitis during the “inflammatory activity state” is crucial for overall prognosis and may avoid the development of dementia in some cases. Based on this case, the authors advocate the concept—long established in many chronic inflammatory diseases in rheumatology—of distinguishing between an “acute inflammatory state” and a “state of organ damage” in autoimmune psychosis resembling neurodegenerative mechanisms.