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Patients with autoimmune encephalitis (AE) often developed psychiatric features during the disease course. Many studies focused on the psychiatric characteristic in anti-NMDAR encephalitis (NMDAR-E), but anti-LGI1 encephalitis (LGI1-E) had received less attention regarding the analysis of psychiatric features, and no study compared psychiatric characteristic between these two groups. The clinical data of AE patients (62 NMDAR-E and 20 LGI1-E) who developed psychiatric symptoms were analyzed in this study. In NMDAR-E, the most common higher-level feature was "behavior changes" (60/62, 96.8%) and the lower-level feature "incoherent speech" was observed in 33 patients (33/62, 53.2%), followed by "agitation" (29/62, 46.8%) and "incongruent laughter/crying" (20/62, 32.3%). Similar to NMDAR-E, "behavior changes" was most common in LGI1-E (17/20, 85.0%), but the features of suicidality, eating, and obsessive–compulsive were not reported. The top three lower-level features were visual hallucinations (9/20, 45.0%), incoherent speech (8/20, 40.0%), and mood instability (7/20, 35.0%). The comparative study found that "incongruent laughter/crying", in lower-level features, was more frequently observed in NMDAR-E (32.3% vs. 0%, p = 0.002). Moreover, the Bush Francis Catatonia Rating Scale (BFCRS) assessing the catatonic symptoms in NMDAR-E were higher than LGI1-E, but the 18 item-Brief Psychiatric Rating Scale (BPRS-18) showed no difference in the two groups. In summary, both NMDAR-E and LGI1-E often developed psychiatric symptoms. In contrast with LGI1-E, the psychiatric feature "incongruent laughter/crying" was more frequently associated with NMDAR-E, and catatonic symptoms were more severe in NMDAR-E. [ABSTRACT FROM AUTHOR]

Pilomotor seizures are strongly associated with autoimmune encephalitis (AE), particularly anti‐LGI1 encephalitis. The carbonic anhydrase inhibitor acetazolamide may have special efficacy for treating AE‐associated pilomotor seizures. Six patients with AE (five anti‐LGI1, one seronegative) and temporal lobe pilomotor seizures (five with seizures inducible by hyperventilation) were treated with acetazolamide, administered in a cycling (2‐days‐ON, 4‐days‐OFF) regimen to offset tolerance. Seizures were assessed during epilepsy monitoring unit (EMU) recordings in four inpatients (one of whom also maintained an outpatient seizure diary chronicling 1203 seizures over 1079 days); two outpatients self‐reported seizure frequencies. The extended diary revealed an inverse correlation between acetazolamide and proportion of seizures/day: 6%, 2% (days 1, 2 ON); 3%, 13%, 31%, 45% (days 1, 2, 3, 4 OFF). This patient later developed focal status epilepticus upon wean of antiseizure medications during a seropositive AE relapse that was remarkably aborted with acetazolamide monotherapy. The other three EMU patients averaged.56 seizures/day ON, and 3.81 seizures/day OFF (p =.004). The two outpatients reported seizure reductions from 3–5/day to 2/week, and 15–20/day to none, respectively, after initiation of cycling acetazolamide. Likely related to cerebral CO2/pH sensitivity, acetazolamide can be unusually effective in controlling pilomotor seizures in AE, chronically or in acute settings. [ABSTRACT FROM AUTHOR]

Background: Mycophenolate mofetil (MMF) is frequently used in the treatment of neurological autoimmune disorders. However, its effect on the relapse risk in anti-leucine-rich glioma–inactivated protein 1 (anti-LGI1) encephalitis is not well studied. Methods: In this prospective observational cohort study, anti-LGI1 encephalitis patients were grouped according to MMF treatment status (MMF and non-MMF groups). The primary outcome was relapse after disease onset. Results: A total of 83 patients were included, with a median onset age of 60 years. Fifty-four patients were men (65.1%). The MMF group comprised 28 patients and the non-MMF group comprised 55. Median follow-up from symptom onset was 26 months. Relapse occurred in 43 patients (51.8%). Median modified Rankin scale (mRS) score at enrollment was significantly higher in the MMF group than the non-MMF group (3 vs. 2; p = 0.001). Median mRS score at last follow-up was comparable between groups (1 vs. zero; p = 0.184). Both MMF treatment (HR 0.463; 95% CI, 0.231–0.929; p = 0.030) and cognitive impairment at enrollment (HR 3.391; 95% CI, 1.041–11.044; p = 0.043) were independent predictors of relapse. Starting immunotherapy before development of cognitive impairment trended towards reducing relapse risk. Outcome at last follow-up was good (mRS score 0–2) in all patients except for one in the non-MMF group. Adverse events associated with MMF treatment were mild and transient. Conclusion: Although the outcome of anti-LGI1 encephalitis patients is generally favorable, relapse is common, especially in those with cognitive impairment. MMF treatment is well-tolerated and can significantly reduce the risk of relapse. [ABSTRACT FROM AUTHOR]

Purpose: TSPO PET with radioligand [18F]DPA-714 is an emerging molecular imaging technique that reflects cerebral inflammation and microglial activation, and it has been recently used in central nervous system diseases. In this study, we aimed to investigate the neuroinflammation pattern of anti-leucine-rich glioma-inactivated 1 (LGI1) protein autoimmune encephalitis (AIE) and to evaluate its possible correlation with clinical phenotypes. Methods: Twenty patients with anti-LGI1 encephalitis from the autoimmune encephalitis cohort in Huashan Hospital and ten with other AIE and non-inflammatory diseases that underwent TSPO PET imaging were included in the current study. Increased regional [18F]DPA-714 retention in anti-LGI1 encephalitis was detected on a voxel basis using statistic parametric mapping analysis. Multiple correspondence analysis and hierarchical clustering were conducted for discriminate subgroups in anti-LGI1 encephalitis. Standardized uptake value ratios normalized to the cerebellum (SUVRc) were calculated for semiquantitative analysis of TSPO PET features between different LGI1-AIE subgroups. Results: Increased regional retention of [18F]DPA-714 was identified in the bilateral hippocampus, caudate nucleus, and frontal cortex in LGI1-AIE patients. Two subgroups of LGI1-AIE patients were distinguished based on the top seven common symptoms. Patients in cluster 1 had a high frequency of facio-brachial dystonic seizures than those in cluster 2 (p = 0.004), whereas patients in cluster 2 had a higher frequency of general tonic–clonic (GTC) seizures than those in cluster 1 (p < 0.001). Supplementary motor area and superior frontal gyrus showed higher [18F]DPA-714 retention in cluster 2 patients compared with those in cluster 1 (p = 0.024; p = 0.04, respectively). Conclusions: Anti-LGI1 encephalitis had a distinctive molecular imaging pattern presented by TSPO PET scan. LGI1-AIE patients with higher retention of [18F]DPA-714 in the frontal cortex were more prone to present with GTC seizures. Further studies are required for verifying its value in clinical application. [ABSTRACT FROM AUTHOR]

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common kind of autoimmune encephalitis following anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Anti-LGI1 encephalitis is characterized by cognitive impairment or rapid progressive dementia, psychiatric disorders, epileptic seizures, faciobrachial dystonic seizures (FBDS), and refractory hyponatremia. Recently, we found an atypical manifestation of anti-LGI1 encephalitis, in which paroxysmal limb weakness was the initial symptom. In this report, we describe five cases of anti-LGI1 encephalitis with paroxysmal limb weakness. Patients had similar presentations, where a sudden weakness involving a unilateral limb was observed, which lasted several seconds and occurred dozens of times each day, with the anti-LGI1 antibody being positive in both serum and cerebrospinal fluid (CSF). FBDS occurred after a mean of 12 days following paroxysmal limb weakness in three of five patients (Cases 1, 4, and 5). All patients were given high-dose steroid therapy, which had a good effect on their condition. Based on this report, we suggest that paroxysmal unilateral weakness may be a kind of epilepsy and be connected to FBDS. As an unusual neurological presentation, paroxysmal weakness can be included in the clinical manifestations of anti-LGI1 encephalitis, helping to raise awareness of the recognition of anti-LGI1 encephalitis in patients with this symptom and leading to early diagnosis and early treatment, which would contribute to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Ever since AE was acknowledged as a potentially treatable cause of encephalitis, it has been increasingly recognised worldwide. Data suggests that these disorders are under-recognized, which calls for an increased awareness of the varying clinical, laboratory, electrophysiological and radiological presentations of the different types of autoimmune encephalitis. This cross-sectional observational study included all patients diagnosed with AE, who presented to a tertiary care centre from June 2016 to January 2021. Data were collected including patient’s demography, clinical, laboratory, radiological and electrophysiology studies, management and outcomes. Results 31 study participants were included, of which 13 patients were anti-NMDA antibody positive, 12 patients were anti-LGI1 antibody positive, 2 patients were anti-CASPR2 antibody positive, 2 were positive for dual positive status (anti-LGi1 and anti-CASPR2), and one each for anti-GABA-B and anti-GAD 65. There was a marginal male predilection with overall seizures being the most common symptom (68%) followed by behavioural disturbance (64.5%), and impairment of consciousness (32.3%). Patients with Anti-NMDA encephalitis were likely to be young females, with CSF pleocytosis, a more protracted hospital course with more chances of relapse and residual disease, while the patients with anti-Lgi1 encephalitis were likely to be older males with a shorter, less severe hospital course. Conclusion The present study detailed the demographic, clinical, imaging, laboratory and EEG characteristics of 31 AE patients from a tertiary centre. The findings concurred with the literature and demonstrate the diverse spectrum of clinical manifestations of patients with AE, present with.

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]

Seizures are the main manifestation of the acute phase of autoimmune encephalitis (AE). Anti-seizure medications (ASMs) play an important role in controlling seizures in AE patients, but there is currently a lack of consensus regarding the selection, application, and discontinuation of ASMs. This narrative review focuses on the use of ASMs in patients with AE driven by different antibodies. The PubMed, Embase, and MEDLINE databases were searched up until 30 October 2022 using prespecified search terms. We identified 2,580 studies; 23 retrospective studies, 2 prospective studies and 9 case reports were evaluated based on our inclusion criteria. Anti-N-methyl-D-aspartic-acid-receptor (anti-NMDAR) encephalitis is the type of AE that responds best to ASMs, and long-term or combined use of ASMs may be not required in most patients with seizures; these results apply to both adults and children. Sodium channel blockers may be the best option for seizures in anti-leucine-rich-glioma-inactivated-1 (anti-LGI1) encephalitis, but patients with anti-LGI1 encephalitis are prone to side effects when using ASMs. Cell surface antibody-mediated AE patients are more likely to use ASMs for a long period than patients with intracellular antibody-mediated AE. Clinicians can score AE patients' clinical characteristics on a scale to identify those who may require long-or shortterm use of ASMs in the early stage. This review provides some recommendations for the rational use of ASMs in encephalitis mediated by different antibodies with the aim of controlling seizures and avoiding overtreatment. [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 Ever since AE was acknowledged as a potentially treatable cause of encephalitis, it has been increasingly recognised worldwide. Data suggests that these disorders are under-recognized, which calls for an increased awareness of the varying clinical, laboratory, electrophysiological and radiological presentations of the different types of autoimmune encephalitis. This cross-sectional observational study included all patients diagnosed with AE, who presented to a tertiary care centre from June 2016 to January 2021. Data were collected including patient's demography, clinical, laboratory, radiological and electrophysiology studies, management and outcomes. Results 31 study participants were included, of which 13 patients were anti-NMDA antibody positive, 12 patients were anti-LGI1 antibody positive, 2 patients were anti-CASPR2 antibody positive, 2 were positive for dual positive status (anti-LGi1 and anti-CASPR2), and one each for anti-GABA-B and anti-GAD 65. There was a marginal male predilection with overall seizures being the most common symptom (68%) followed by behavioural disturbance (64.5%), and impairment of consciousness (32.3%). Patients with Anti-NMDA encephalitis were likely to be young females, with CSF pleocytosis, a more protracted hospital course with more chances of relapse and residual disease, while the patients with anti-Lgi1 encephalitis were likely to be older males with a shorter, less severe hospital course. Conclusion The present study detailed the demographic, clinical, imaging, laboratory and EEG characteristics of 31 AE patients from a tertiary centre. The findings concurred with the literature and demonstrate the diverse spectrum of clinical manifestations of patients with AE, present with. [ABSTRACT FROM AUTHOR]

In autoimmune encephalitis, abnormalities of diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), arterial spin labeling (ASL) in magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) have been reported. However, there are few studies of long-term follow-up of imaging. We report a case of anti-leucine-rich glioma-inactivated 1 antibody encephalitis whose MRI (DWI, FLAIR and ASL), 99mTcHM-PAO SPECT (PAO-SPECT) and 18F-FDG-PET were evaluated through the clinical course. ASL, PAO-SPECT and 18F-FDG-PET consistently showed abnormalities in almost the same area. Serial assessment of these imaging modalities is useful in evaluating disease activity and efficacy of treatment.

Over the past decade, cancer immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved the outcome of many malignancies. However, with the broad use of ICIs, neurological immune related adverse events (irAE) are increasingly recognized. ICI-induced encephalitis (ICI-iE) is a particularly severe irAE, often leading to treatment termination, long-term sequalae or death. Despite its high morbidity and mortality, data on clinical features and diagnostic criteria are limited.We aimed to define clinical, radiologic and laboratory characteristics of ICI-iE and identify factors that discriminate it from anti-leucine-rich glioma-inactivated (anti-LGI)-1 encephalitis and herpes simplex virus (HSV)-1 encephalitis – two alternative causes of encephalitis – to increase the awareness of ICI-iE and improve its diagnosis and management.To that end, we retrospectively collected 30 cases of ICI-iE that were reported to the Side Effect Registry Immuno-Oncology (SERIO) and 46 cases of anti-LGI1 encephalitis or herpes simplex virus (HSV)-1 encephalitis that presented to a large German neurological referral center (Charité Universitätsmedizin Berlin) between January 2015 and September 2021. Signs and symptoms, imaging and electroencephalogram features, laboratory findings and outcome measures were assessed using standardized case report forms as well as patients’ medical records and compared between the groups.The data reported here represents the largest primary cohort of patients with ICI-iE to date and the first comparison with other types of encephalitis. As all three disorders – ICI-iE, HSV-1 encephalitis and anti-LGI1 encephalitis – are rare neurological entities, this dataset can be used as a reference in future clinical studies on ICI-induced neurotoxicity, neurological autoimmune disorders, and central nervous system infections.

Immune checkpoint inhibitor-induced encephalitis (ICI-iE) is a rare but life-threatening toxicity of immune checkpoint inhibitor treatment. We aim to identify the characteristics of ICI-iE and describe factors that discriminate it from herpes simplex virus (HSV)-1 encephalitis and anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis, as two alternative entities of encephalitis. In this retrospective multicentre cohort study, we collected patients with ICI-iE reported to the Side Effect Registry Immuno-Oncology from January 2015 to September 2021 and compared their clinical features and outcome with 46 consecutive patients with HSV-1 or anti-LGI1 encephalitis who were treated at a German neurological referral centre. Thirty cases of ICI-iE, 25 cases of HSV-1 encephalitis and 21 cases of anti-LGI1 encephalitis were included. Clinical presentation of ICI-iE was highly variable and resembled that of HSV-1 encephalitis, while impairment of consciousness (66% vs. 5%, p =.007), confusion (83% vs. 43%; p =.02), disorientation (83% vs. 29%; p =.007) and aphasia (43% vs. 0%; p =.007) were more common in ICI-iE than in anti-LGI1 encephalitis. Antineuronal antibodies (17/18, 94%) and MRI (18/30, 60%) were mostly negative in ICI-iE, but cerebrospinal fluid (CSF) showed pleocytosis and/or elevated protein levels in almost all patients (28/29, 97%). Three patients (10%) died of ICI-iE. Early immunosuppressive treatment was associated with better outcome (r = 0.43). ICI-iE is a heterogeneous entity without specific clinical features. CSF analysis has the highest diagnostic value, as it reveals inflammatory changes in most patients and enables the exclusion of infection. Early treatment of ICI-iE is essential to prevent sequelae and death. • Presentation of ICI-iE is variable and resembles that of HSV-1 encephalitis. • Abnormal MRI and antineuronal antibodies are less common than previously reported. • Analysis of cerebrospinal fluid has the highest diagnostic value in ICI-iE. • ICI-iE has a mortality of 10% and long-term sequelae occur in 47% of patients. • Early immunosuppressive treatment of ICI-iE is associated with full recovery. [ABSTRACT FROM AUTHOR]

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common cause of autoimmune encephalitis and is characterized by cognitive impairment, psychiatric disorders, and faciobrachial dystonic seizures. In recent decades, literature reports have expanded the phenotypic spectrum associated with the LGI1 autoantibody. The present report describes the case of a 58-yearold man who presented with repetitive unilateral hyperhidrosis of the body and arm as an initial symptom and gradually developed psychiatric symptoms, involuntary movements of the face and arms, and progressive cognitive decline. Anti-LGI1 antibodies were positive in both the serum and cerebrospinal fluid at approximately 2 months after symptom onset, and the patient was, therefore, diagnosed with anti-LGI1 encephalitis. His symptoms, namely hyperhidrosis and involuntary movements, were not relieved by antiepileptic drug treatment, but responded favorably to high-dose steroid therapy and intravenous immunoglobulin. We interpreted the repetitive unilateral hyperhidrosis as possible epilepsy. Based on this case, unilateral hyperhidrosis of the body and arm as a rare neurological presentation can be added to the phenotypic spectrum of anti-LGI1 encephalitis, and early recognition of this manifestation might support timely diagnosis and treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Anti-LGI1 and anti-CASPR2 encephalitis had similar clinical manifestations. • Patients with VGKC antibody-associated diseases responded well to immunotherapy. • These patients also had favorable clinical outcomes. • ICU-admitted people with high mRS score at onset and dyskinesia have poor outcome. The present study aimed to investigate the clinical manifestations, epidemiological characteristics, and outcomes of Chinese patients with voltage-gated potassium channel complex (VGKC) antibody – associated encephalitis. Patients diagnosed with VGKC antibody-associated encephalitis at our institution between January 2016 and December 2020 were included in this study. We retrospectively evaluated their clinical features, auxiliary examination results, treatments details, long-term outcomes, and risk factors for poor outcome. Of the 91 included patients, 61 (67.78%) were men and 30 (32.97%) were women. The most common clinical symptoms were seizures (n = 63, 69.23%), memory deficits (n = 62, 68.13%), mental behavioral disorders (n = 29, 31.87%), and hyponatremia (n = 57, 62.64%). Although patients with anti- leucine-rich glioma-inactivated 1 (LGI1) (n = 76) and anti- contactin-associated protein-like 2 (CASPR2) encephalitis (n = 15) had similar clinical manifestations, the former were more diverse. In total, 86 (94.51%) patients were treated with immunotherapy. Over a median follow-up period of 25 months, there were no mortalities and 14 (15.38%) patients experienced a relapse. Univariate analysis indicated differences in sex, modified Rankin Scale scores at onset, movement disorders, central hypoventilation, and intensive care unit occupancy between the good- and poor- outcome groups. Patients with anti-LGI1 and anti-CASPR2 encephalitis showed similar clinical manifestations while presenting delineating characteristics. Those with VGKC antibody-associated diseases generally responded well to immunotherapy and demonstrated favorable clinical outcomes. Several factors affected the prognosis, and a long-term follow-up examination is necessary. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relapse rate and study the factors that may predict the subsequent relapse in anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis in Northeast China. Methods: In the retrospective cohort study, we consecutively enrolled patients with anti-N1MDAR, anti-GABABR and anti-LGI1 encephalitis between March 2015 and November 2021. The patients were followed up for at least 6 months. The outcome variable was a binary variable of relapse or not. Predictors of relapse were identified. Results: A total of 100 patients were enrolled. Relapse occurred in 26 (26%) patients after a median follow-up of 18 months since the first event. The relapse rates of anti - NMDAR, anti - GABABR and anti - LGI1 encephalitis were 25%, 33.3%, and 28.6%, respectively. The multivariable analysis results suggested that immunotherapy delay at the acute phase was independently associated with an increased risk of relapse in total patients (HR = 2.447, 95% CI = 1.027 - 5.832; P = 0.043). Subgroup analysis results showed that antibody titer was associated with the likelihood of relapse in anti-LGI1 encephalitis. The higher the concentration, the more likely it was for patients to have relapse (p=0.019). Conclusion: The general relapse rate of anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis was 26%. The risk of subsequent relapse was elevated in those with delayed immunotherapy in the first episode. In subgroup of anti-LGI1 encephalitis, higher antibody titer was the risk factors of relapse. Thus, timely and aggressive immunotherapy may be beneficial for patients to prevent subsequent relapse. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the relapse rate and study the factors that may predict the subsequent relapse in anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis in Northeast China.MethodsIn the retrospective cohort study, we consecutively enrolled patients with anti-N1MDAR, anti-GABABR and anti-LGI1 encephalitis between March 2015 and November 2021. The patients were followed up for at least 6 months. The outcome variable was a binary variable of relapse or not. Predictors of relapse were identified.ResultsA total of 100 patients were enrolled. Relapse occurred in 26 (26%) patients after a median follow-up of 18 months since the first event. The relapse rates of anti - NMDAR, anti - GABABR and anti - LGI1 encephalitis were 25%, 33.3%, and 28.6%, respectively. The multivariable analysis results suggested that immunotherapy delay at the acute phase was independently associated with an increased risk of relapse in total patients (HR = 2.447, 95% CI = 1.027 - 5.832; P = 0.043). Subgroup analysis results showed that antibody titer was associated with the likelihood of relapse in anti-LGI1 encephalitis. The higher the concentration, the more likely it was for patients to have relapse (p=0.019).ConclusionThe general relapse rate of anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis was 26%. The risk of subsequent relapse was elevated in those with delayed immunotherapy in the first episode. In subgroup of anti-LGI1 encephalitis, higher antibody titer was the risk factors of relapse. Thus, timely and aggressive immunotherapy may be beneficial for patients to prevent subsequent relapse.

We report a 77-year-old woman with a thymoma, anti-LGI1antibody associated encephalitis (LGI1 encephalitis), and MG accompanied by positive anti-acetylcholine receptor antibodies (AchR Ab) and anti-titin antibodies (titin Ab). She was treated with thymomectomy followed by immunosuppressive therapy, which resulted in immediate amelioration of motor weakness and gradual improvement of cognitive impairment over the next two years. LGI1 Ab were positive at two months after thymomectomy, followed by negative conversion demonstrated on 1 year examination. The AchR Ab level had gradually decreased but titin Ab was positive on re-examination after two years, although the cognition and motor impairment symptoms had been alleviated. In patients with suspected autoimmune encephalitis, the detection of several autoantibodies including LGI1 and thymomas provides useful information for making an accurate diagnosis.

Objective: This study aims to detect the invisible metabolic abnormality in PET images of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis using a multivariate cross-classification method. Methods: Participants were divided into two groups, namely, the training cohort and the testing cohort. The training cohort included 17 healthy participants and 17 patients with anti-LGI1 encephalitis whose metabolic abnormality was able to be visibly detected in both the medial temporal lobe and the basal ganglia in their PET images [completely detectable (CD) patients]. The testing cohort included another 16 healthy participants and 16 patients with anti-LGI1 encephalitis whose metabolic abnormality was not able to be visibly detected in the medial temporal lobe and the basal ganglia in their PET images [non-completely detectable (non-CD) patients]. Independent component analysis (ICA) was used to extract features and reduce dimensions. A logistic regression model was constructed to identify the non-CD patients. Results: For the testing cohort, the accuracy of classification was 90.63% with 13 out of 16 non-CD patients identified and all healthy participants distinguished from non-CD patients. The patterns of PET signal changes resulting from metabolic abnormalities related to anti-LGI1 encephalitis were similar for CD patients and non-CD patients. Conclusion: This study demonstrated that multivariate cross-classification combined with ICA could improve, to some degree, the detection of invisible abnormal metabolism in the PET images of patients with anti-LGI1 encephalitis. More importantly, the invisible metabolic abnormality in the PET images of non-CD patients showed patterns that were similar to those seen in CD patients. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the mortality rate and identify the predictors of death in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis. Methods: Patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis were recruited from the Neurology Department of the First Hospital of Jilin University from March 2015 to November 2021. The primary outcome variable was a binary variable of death vs. survival. The potential risk factors for mortality were evaluated. The mortality rates were determined, and the independent predictors of death were identified using multivariable logistic regression analysis. Results: A total of 100 hospitalized patients with anti-NMDAR, anti-LGI1, or anti-GABABR encephalitis were included in the final analysis. Fifteen patients (15%) died during a median follow-up period of 18 months. The mortality rates were 10% for anti-NMDAR encephalitis, 2.8% for anti-LGI1 encephalitis, and 41.7% for anti-GABABR encephalitis. The multivariable analysis results showed that older age at onset [adjusted odds ratio (OR) = 1.017, 95% confidence interval (CI) = 1.009–1.136; p = 0.023] was independently associated with an increased risk of death. Antibody type was also associated with mortality. Patients with anti-GABABR encephalitis had 13.458-fold greater odds of dying than patients with anti-LGI1 encephalitis (adjusted OR = 13.458, 95% CI = 1.270–142.631; p = 0.031). Conclusion: The general mortality rate of anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis was 15%. Age at onset and type of autoimmune encephalitis antibody were independent predictors of death in these patients. [ABSTRACT FROM AUTHOR]

Shan Qiao,1 Huai-kuan Wu,1 Ling-ling Liu,2 Mei-ling Wang,3 Ran-ran Zhang,4 Tao Han,5 Xue-wu Liu4 1Department of Neurology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong Province 250014, People’s Republic of China; 2Department of Neurology, Liaocheng People’s Hospital, Liaocheng, Shandong Province 252000, People’s Republic of China; 3Department of Neurology, Binzhou Medical University Hospital, Binzhou, Shandong Province 256603, People’s Republic of China; 4Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, People’s Republic of China; 5Department of Neurology, Shandong Provincial Hospital, Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Xue-wu LiuDepartment of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 Wen Hua Xi Road, Jinan 250012, Shan Dong, People’s Republic of ChinaTel + 86 0531-82169114Email snlxw1966@163.comPurpose: To describe the clinical manifestation, immunotherapy, and long-term outcomes of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.Patients and Methods: This study was a retrospective analysis of 117 patients with a diagnosis of anti-LGI1 encephalitis identified from the databases of multiple clinical centers between September 2014 and December 2019. The clinical features, ancillary test results, and details of long-term outcomes were evaluated.Results: Among the 117 patients with anti-LGI1 encephalitis, 69.2% (81/117) were male and 30.8% (36/117) were female. The median age of all patients at the onset of the disease was 57 years (interquartile range [IQR], 52– 67). The median time from symptom onset to diagnosis was 8.7 weeks (IQR, 4.2– 25). The main clinical features identified were seizures, cognitive impairment, and mental and behavioral abnormalities. Of the 117 patients, 109 were treated with immunotherapy. Symptoms including memory, mental ability, and behavior improved in all 109 patients after 3– 5 days of treatment. The median time of follow-up for the treated patients was 33 months (IQR, 17– 42). Of the treated patients, 16.2% (19/117) experienced a relapse, with a median delay of 5 months (IQR, 2.1– 17) between onset and the first relapse. There were no mortalities over the follow-up period.Conclusion: The long-term outcome of patients with anti-LGI1 encephalitis was mostly favorable, although some patients continued to experience cognitive dysfunction. Early recognition is important for prompt initiation of immunotherapy that can improve clinical symptoms of anti-LGI1 encephalitis.Keywords: anti-LGI1 encephalitis, autoimmune epilepsy, follow-up, immunotherapy, relapse

ObjectiveThis study aims to detect the invisible metabolic abnormality in PET images of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis using a multivariate cross-classification method.MethodsParticipants were divided into two groups, namely, the training cohort and the testing cohort. The training cohort included 17 healthy participants and 17 patients with anti-LGI1 encephalitis whose metabolic abnormality was able to be visibly detected in both the medial temporal lobe and the basal ganglia in their PET images [completely detectable (CD) patients]. The testing cohort included another 16 healthy participants and 16 patients with anti-LGI1 encephalitis whose metabolic abnormality was not able to be visibly detected in the medial temporal lobe and the basal ganglia in their PET images [non-completely detectable (non-CD) patients]. Independent component analysis (ICA) was used to extract features and reduce dimensions. A logistic regression model was constructed to identify the non-CD patients.ResultsFor the testing cohort, the accuracy of classification was 90.63% with 13 out of 16 non-CD patients identified and all healthy participants distinguished from non-CD patients. The patterns of PET signal changes resulting from metabolic abnormalities related to anti-LGI1 encephalitis were similar for CD patients and non-CD patients.ConclusionThis study demonstrated that multivariate cross-classification combined with ICA could improve, to some degree, the detection of invisible abnormal metabolism in the PET images of patients with anti-LGI1 encephalitis. More importantly, the invisible metabolic abnormality in the PET images of non-CD patients showed patterns that were similar to those seen in CD patients.

ObjectiveWe aimed to investigate the mortality rate and identify the predictors of death in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis.MethodsPatients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis were recruited from the Neurology Department of the First Hospital of Jilin University from March 2015 to November 2021. The primary outcome variable was a binary variable of death vs. survival. The potential risk factors for mortality were evaluated. The mortality rates were determined, and the independent predictors of death were identified using multivariable logistic regression analysis.ResultsA total of 100 hospitalized patients with anti-NMDAR, anti-LGI1, or anti-GABABR encephalitis were included in the final analysis. Fifteen patients (15%) died during a median follow-up period of 18 months. The mortality rates were 10% for anti-NMDAR encephalitis, 2.8% for anti-LGI1 encephalitis, and 41.7% for anti-GABABR encephalitis. The multivariable analysis results showed that older age at onset [adjusted odds ratio (OR) = 1.017, 95% confidence interval (CI) = 1.009–1.136; p = 0.023] was independently associated with an increased risk of death. Antibody type was also associated with mortality. Patients with anti-GABABR encephalitis had 13.458-fold greater odds of dying than patients with anti-LGI1 encephalitis (adjusted OR = 13.458, 95% CI = 1.270–142.631; p = 0.031).ConclusionThe general mortality rate of anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis was 15%. Age at onset and type of autoimmune encephalitis antibody were independent predictors of death in these patients.

Objective: To analyze the clinical features of common autoimmune encephalitis and evaluate the sensitivity of antibodies contributing to focal epilepsy signs and symptoms (ACES) score. Methods: Collecting and analyzing the data of 242 patients with autoimmune encephalitis (AE) diagnosed in the First Affiliated Hospital of Zhengzhou University from August 2015 to December 2020 in this retrospective study. The six items of the ACES score (cognitive symptoms, behavioral changes, autonomic symptoms, speech problems, autoimmune diseases, temporal MRI hyperintensities) were screened in patients with complete clinical data. Results: (1) In total, 242 patients were included, with 147 cases of anti-N-methyl-D-aspartate receptor encephalitis, 47 cases of anti-γ-aminobutyric acid type B (GABA-B) receptor encephalitis, and 48 cases of anti-leucine-rich glioma inactivating protein 1 (LGI1) encephalitis. The most common clinical symptoms are cognitive impairment (77%), behavioral changes (79%), and seizures (71%). In total, 129 cases (54%) combined with autonomic dysfunction, such as gastrointestinal dysmotility, sinus tachycardia, and central hypoventilation. Twelve patients had autoimmune diseases, most of which were of thyroid diseases. (2) One hundred and twenty-seven patients with complete clinical data evaluated ACES score, 126 cases of whom (126/127, 99.2%) were equal to or >2 points, 1 case (1/127, 0.8%) was of <2 points. Interpretation: (1) Cognitive impairment, abnormal behavior, and seizures are the most common manifestations of AE and autonomic symptoms. Thyroid disease is the most autoimmune disease in AE. Clinically, for patients of suspected AE, increasing the knowledge and testing of thyroid function and rheumatism is necessary. (2) ACES score is a simple, effective, and easy-to-operate score, with a certain screening value for most patients suspected of AE. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical features of common autoimmune encephalitis and evaluate the sensitivity of antibodies contributing to focal epilepsy signs and symptoms (ACES) score.Methods: Collecting and analyzing the data of 242 patients with autoimmune encephalitis (AE) diagnosed in the First Affiliated Hospital of Zhengzhou University from August 2015 to December 2020 in this retrospective study. The six items of the ACES score (cognitive symptoms, behavioral changes, autonomic symptoms, speech problems, autoimmune diseases, temporal MRI hyperintensities) were screened in patients with complete clinical data.Results: (1) In total, 242 patients were included, with 147 cases of anti-N-methyl-D-aspartate receptor encephalitis, 47 cases of anti-γ-aminobutyric acid type B (GABA-B) receptor encephalitis, and 48 cases of anti-leucine-rich glioma inactivating protein 1 (LGI1) encephalitis. The most common clinical symptoms are cognitive impairment (77%), behavioral changes (79%), and seizures (71%). In total, 129 cases (54%) combined with autonomic dysfunction, such as gastrointestinal dysmotility, sinus tachycardia, and central hypoventilation. Twelve patients had autoimmune diseases, most of which were of thyroid diseases. (2) One hundred and twenty-seven patients with complete clinical data evaluated ACES score, 126 cases of whom (126/127, 99.2%) were equal to or >2 points, 1 case (1/127, 0.8%) was of

ObjectiveThis single-center study was conducted in a cohort of patients with anti-LGI1 encephalitis to investigate the factors related to their functional recovery.MethodsWe retrospectively collected the clinical information of patients admitted to Xuanwu Hospital from January 2014 until December 2019, and followed up for at least 12 months.ResultsA total of 67 patients were included, and 57 completed the 12-month follow-up. Most of the patients (55/57, 96.5%) achieved functional improvement after immunotherapy, and 26 (45.6%) became symptom-free. Compared to patients with complete recovery, patients with partial or no recovery had significantly higher incidences of consciousness disorders (25.8% vs. 0%, P

• The ONES checklist showed better sensitivity than the APE2 score. • Specificity of the two assessment tools was similar. • Both assessment tools performed less well in predicting the presence of LGI1-Abs when compared to NMDAR-Abs. The identification of patients with seizures of unknown etiology who would benefit from neural antibody testing necessitates effective assessment tools. The study aimed to compare the performance of the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score and the "Obvious" Indications for Neural Antibody Testing in Epilepsy or Seizures (ONES) checklist. We also intended to evaluate whether the performance of the tools varied by types of antibody. Patients diagnosed with epilepsy, seizures, or status epilepticus of unknown etiology at West China Hospital from January 2019 to December 2021 were included. Paired serum/cerebrospinal fluid samples were analyzed for antineuronal and antiglial antibodies. The APE2 score and ONES checklist were applied, and their outcomes were compared to laboratory antibody test results. Possible false positive neuronal antibody results were excluded in sensitivity/specificity analysis reasonably. A total of 113 antibody-positive and 159 antibody-negative patients were enrolled in sensitivity/specificity analysis. The ONES checklist showed superior sensitivity than APE2 score (95.6 % vs.79.6 %, P < 0.001). Specificity was not statistically different (60.4 % vs. 57.9 %, P = 0.557). The negative predictive value (NPV) of ONES checklist was higher than that of APE2 score (94.8 % vs 80.7 %, P < 0.001). The positive predictive value of them was not statistically different (61.7 % vs 58.8 %, P = 0.557). APE2 score exhibited lower sensitivity for predicting LGI-Abs (52.9 % vs. 80.3 %, P = 0.022) compared to NMDAR-Abs. Similarly, ONES checklist showed lower sensitivity for LGI1-Abs than NMDAR-Abs (82.4 % vs. 100.0 %, P = 0.009). The ONES checklist demonstrates superior sensitivity for neural antibody positivity than APE2 score. Specificity of the two assessment tools was similar. ONES checklist performed better NPV than the APE2 score. Both assessment tools performed less well in predicting the presence of LGI1- Abs when compared to NMDAR-Abs. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune encephalitis is a disorder associated with antibodies directed against central nervous system proteins with variable clinical features. This study aims to add to knowledge of the disease by reporting the details of a cohort of patients with autoimmune encephalitis in Queensland, Australia.Methodology: We surveyed patients with autoimmune encephalitis diagnosed and managed through public hospitals in Queensland, Australia between 2010 and the end of 2019. Cases were identified via case detection through a centralized diagnostic neuroimmunology laboratory (Division of Immunology, HSQ Pathology Queensland Central Laboratory, Brisbane, Queensland, Australia) and a survey of neurologists. Data including demographic details, clinical presentation, investigation results, treatments including immune therapy and outcomes was collected.Results: Sixty cases of antibody positive autoimmune encephalitis were identified. Twenty-eight were of anti-NMDA-receptor encephalitis with other cases associated with antibodies against LGi1, Caspr2, glycine receptor, DPPX, GABAB receptor, IgLON5, GFAP, and SOX1. The number of diagnosed cases, especially of anti-NMDA-receptor encephalitis has markedly increased over the period 2017 to 2019. Clinical presentations were marked by heterogeneous symptom complexes and prolonged hospital admissions. Imaging studies were largely normal or non-specific. There was a response to immune therapy and a low mortality rate. Most cases affected by this disorder were left with ongoing symptoms associated with mild disability.Conclusion: Autoimmune encephalitis in Queensland, Australia is an increasingly common but complex clinical entity marked by heterogeneous presentations, response to immune therapy and outcome results marked by low mortality and incomplete recovery.

Autoimmune encephalitis associated with antibodies against leucine-rich glioma inactivated protein (LGI1) is classically associated with brief, recurrent, contractions of facial and upper limb muscles, typically on the same side. Commonly described as ‘faciobrachial dystonic seizures’ (FBDS), these seizures have become the semiological hallmark of anti-LGI1 encephalitis. However, the facial and upper limb contractions observed in patients with anti-LGI1 encephalitis associated seizures are not always dystonic in nature. Here, we briefly highlight the case of a patient who was admitted to our institution with faciobrachial tonic-myoclonic seizures to emphasize the fact that faciobrachial seizures in anti-LGI1 encephalitis are not always dystonic. We also review the literature on the semiology of these seizures in patients diagnosed with anti-LGI1 encephalitis and propose a more apt description for this phenomenon. Our case as well as the literature highlights that in anti-LGI1 encephalitis the typical seizure semiology of faciobrachial distribution includes tonic, clonic, dystonic, and myoclonic activity in isolation or combination with or without plus features. Given that accurate labelling of clinical phenomenology enables a better understanding of the underlying epileptic networks and precise diagnosis, we would suggest a more inclusive term ‘faciobrachial motor seizures’ instead of ‘faciobrachial dystonic seizures’ to describe the typical seizure semiology of anti-LGI1 encephalitis. Based on the presence or absence of specific clinical features, these seizures can be further sub-classified as focal aware faciobrachial motor seizures, focal impaired awareness faciobrachial motor seizures or focal faciobrachial motor plus seizures (aware or impaired awareness).

Introduction: Autoimmune encephalitis is a disorder associated with antibodies directed against central nervous system proteins with variable clinical features. This study aims to add to knowledge of the disease by reporting the details of a cohort of patients with autoimmune encephalitis in Queensland, Australia. Methodology: We surveyed patients with autoimmune encephalitis diagnosed and managed through public hospitals in Queensland, Australia between 2010 and the end of 2019. Cases were identified via case detection through a centralized diagnostic neuroimmunology laboratory (Division of Immunology, HSQ Pathology Queensland Central Laboratory, Brisbane, Queensland, Australia) and a survey of neurologists. Data including demographic details, clinical presentation, investigation results, treatments including immune therapy and outcomes was collected. Results: Sixty cases of antibody positive autoimmune encephalitis were identified. Twenty-eight were of anti-NMDA-receptor encephalitis with other cases associated with antibodies against LGi1, Caspr2, glycine receptor, DPPX, GABAB receptor, IgLON5, GFAP, and SOX1. The number of diagnosed cases, especially of anti-NMDA-receptor encephalitis has markedly increased over the period 2017 to 2019. Clinical presentations were marked by heterogeneous symptom complexes and prolonged hospital admissions. Imaging studies were largely normal or non-specific. There was a response to immune therapy and a low mortality rate. Most cases affected by this disorder were left with ongoing symptoms associated with mild disability. Conclusion: Autoimmune encephalitis in Queensland, Australia is an increasingly common but complex clinical entity marked by heterogeneous presentations, response to immune therapy and outcome results marked by low mortality and incomplete recovery. [ABSTRACT FROM AUTHOR]

Abstract Aim We aim to review the literature to collate and describe features of encephalitides arising from autoantibodies against leucine‐rich glioma‐inactivated 1 (LGI1), gamma aminobutyric acid receptor (GABABR), and contactin‐associated protein‐like 2 (CASPR2) in Asian populations and compare them with findings of Western studies. Methods Peer‐reviewed articles published till 24 May 2020 were searched, and original, full‐text studies from Asia with serum/CSF antibody‐based diagnosis and at least 2 patients were selected. Twenty‐four studies with 263 patients (139 anti‐LGI1, 114 anti‐GAGABR, and 10 anti‐CASPR2) were included. Data were pooled to produce descriptive information on demographics, clinical characteristics, diagnostics, treatments, and outcome. Results The mean age was 54.2 (anti‐LGI1), 55.2 (anti‐GABABR), and 47.7 years (anti‐CASPR2), with an overall male predominance of 62.0%. Commonest clinical features across all types were seizures (87.5%), memory deficits (80.7%), psychiatric disturbances (75.9%), and altered consciousness (52.9%). Four anti‐LGI1, 40 anti‐GABABR, and 1 anti‐CASPR2 patients had tumors. CSF, MRI, and EEG were abnormal in 33.3%, 54.1%, and 75% patients in anti‐LGI1; 60.0%, 49.6%, and 85.7% in anti‐GABABR; and 50%, 44.4%, and 100% in anti‐CASPR2 patients, respectively. 95.6% patients received first‐line therapy alone (steroids/IVIG/Plasma therapy), and 4.4% received second‐line therapy (rituximab/cyclophosphamide). 91.7%, 63.6%, and 70% of patients had favorable outcomes (modified Rankin Score 0–2) with mortality rates at 2.5%, 23.2%, and 0% in the three types, respectively. Conclusion Our findings suggest that these disorders present in Asian patients at a relatively young age often with features of seizures, memory deficits, and psychiatric disturbances and usually demonstrate a favorable clinical outcome.

Introduction: Anti-leucine-rich glioma-inactivated 1 antibody (anti-LGI1) encephalitis is one of the most common autoimmune encephalitis. Anti-LGI1 encephalitis presented with subacute or acute onset of cognitive impairment, psychiatric disturbances, faciobrachial dystonic seizures (FBDSs), convulsions, and hyponatremia. The common sequela of anti-LGI1 encephalitis is cognitive disorder, but there are few studies on the recovery of cognitive function after immunotherapy. This study aimed to explore clinical characteristics of cognitive impairment and 1-year outcome in patients with anti-LGI1 encephalitis.Methods: The clinical data and characteristics of cognitive impairment of 21 patients with anti-LGI1 encephalitis from 2016 to 2019 in Nanjing Brain Hospital were analyzed retrospectively. At the time of onset of hospitalization and 1 year after discharge, the cognitive functions in these patients were assessed using two cognitive screening scales—Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Basic (MoCA-B).Results: Among the 21 patients, 13 were male and 8 were female, aged 51.10 ± 14.69 (age range 20–72) years. Nineteen patients, comprising 90.48%, had recent memory deterioration. Routine electroencephalography (EEG) results of 13 cases were abnormal. EEG results were epileptic or slow-wave activity involving the temporal lobes. Eleven cases of brain MRI were abnormal, and the focus involved the hippocampus and mediotemporal lobe. The decrease of short-term memory [recall scores: 0.57 ± 0.81 (MMSE), 0.76 ± 1.34 (MoCA-B)] is the most obvious at the time of admission. After intravenous (IV) injection of methylprednisolone and/or immunoglobulin, the clinical symptoms of the patients improved obviously. Total MMSE and MoCA-B scores of patients were significant increased after 1 year (21.19 ± 3.54 vs. 26.10 ± 3.02, P < 0.001; and 19.00 ± 4.38 vs. 25.19 ± 4.25, P < 0.001, respectively). Recall scores and orientation scores of MoCA-B were significantly improved after 1 year (0.76 ± 1.34 vs. 3.24 ± 1.48, P < 0.001; and 3.10 ± 1.26 vs. 5.00 ± 1.22, P < 0.001, respectively). However, 3/21 (14.29%) patients still have obvious short-term memory impairment (recall scores ≤ 1).Conclusion: Cognitive impairment is one of the most common manifestations of anti-LGI1 encephalitis, with the main prominent being acute or subacute short-term memory loss. Although most patients with anti-LGI1 encephalitis respond well to immunotherapy, a small number of patients still have cognitive disorders, mainly recent memory impairment, after 1 year.

Objective: The purpose of this study was to examine the neural substrates and mechanisms that generate memory deficits, seizures and neuropsychiatric abnormalities in encephalitis with LGI1 antibodies using a data-driven, multimodal magnetic resonance imaging (MRI) approach.Methods: Functional MRI data were acquired from 14 anti-LGI1 encephalitis patients and 14 age and gender matched normal controls. Independent component analysis with hierarchical partner matching (HPM-ICA) was used to assess the whole-brain intrinsic functional connectivity. Granger causality (GC) was applied to investigate the effective connectivity among the brain regions that identified by HPM-ICA. Diffusion tensor imaging (DTI) was utilized to investigate white matter microstructural changes of the patients.Results: Participants with LGI1 antibodies encephalitis presented reduced functional connectivity in the brain areas associated with memory, cognition and motion circuits, while increased functional connectivity in putamen and caudate in comparison to the normal controls. Moreover, the effective connectivity in patients was decreased from the frontal cortex to supplementary motor area. Finally, patients had significant reductions in fractional anisotropy (FA) for the corpus callosum, internal capsule, corona radiata and superior longitudinal fasciculus, accompanied by increases in mean diffusivity (MD) for these regions as compared to controls.Conclusion: Our findings suggest that the neural disorder and behavioral deficits of anti-LGI1 encephalitis may be associated with extensive changes in brain connectivity and microstructure. These pathological alterations affect the basal ganglia and limbic system besides the temporal and frontal lobe.

Aim: We aim to review the literature to collate and describe features of encephalitides arising from autoantibodies against leucine‐rich glioma‐inactivated 1 (LGI1), gamma aminobutyric acid receptor (GABABR), and contactin‐associated protein‐like 2 (CASPR2) in Asian populations and compare them with findings of Western studies. Methods: Peer‐reviewed articles published till 24 May 2020 were searched, and original, full‐text studies from Asia with serum/CSF antibody‐based diagnosis and at least 2 patients were selected. Twenty‐four studies with 263 patients (139 anti‐LGI1, 114 anti‐GAGABR, and 10 anti‐CASPR2) were included. Data were pooled to produce descriptive information on demographics, clinical characteristics, diagnostics, treatments, and outcome. Results: The mean age was 54.2 (anti‐LGI1), 55.2 (anti‐GABABR), and 47.7 years (anti‐CASPR2), with an overall male predominance of 62.0%. Commonest clinical features across all types were seizures (87.5%), memory deficits (80.7%), psychiatric disturbances (75.9%), and altered consciousness (52.9%). Four anti‐LGI1, 40 anti‐GABABR, and 1 anti‐CASPR2 patients had tumors. CSF, MRI, and EEG were abnormal in 33.3%, 54.1%, and 75% patients in anti‐LGI1; 60.0%, 49.6%, and 85.7% in anti‐GABABR; and 50%, 44.4%, and 100% in anti‐CASPR2 patients, respectively. 95.6% patients received first‐line therapy alone (steroids/IVIG/Plasma therapy), and 4.4% received second‐line therapy (rituximab/cyclophosphamide). 91.7%, 63.6%, and 70% of patients had favorable outcomes (modified Rankin Score 0–2) with mortality rates at 2.5%, 23.2%, and 0% in the three types, respectively. Conclusion: Our findings suggest that these disorders present in Asian patients at a relatively young age often with features of seizures, memory deficits, and psychiatric disturbances and usually demonstrate a favorable clinical outcome. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to examine the neural substrates and mechanisms that generate memory deficits, seizures and neuropsychiatric abnormalities in encephalitis with LGI1 antibodies using a data-driven, multimodal magnetic resonance imaging (MRI) approach. Methods: Functional MRI data were acquired from 14 anti-LGI1 encephalitis patients and 14 age and gender matched normal controls. Independent component analysis with hierarchical partner matching (HPM-ICA) was used to assess the whole-brain intrinsic functional connectivity. Granger causality (GC) was applied to investigate the effective connectivity among the brain regions that identified by HPM-ICA. Diffusion tensor imaging (DTI) was utilized to investigate white matter microstructural changes of the patients. Results: Participants with LGI1 antibodies encephalitis presented reduced functional connectivity in the brain areas associated with memory, cognition and motion circuits, while increased functional connectivity in putamen and caudate in comparison to the normal controls. Moreover, the effective connectivity in patients was decreased from the frontal cortex to supplementary motor area. Finally, patients had significant reductions in fractional anisotropy (FA) for the corpus callosum, internal capsule, corona radiata and superior longitudinal fasciculus, accompanied by increases in mean diffusivity (MD) for these regions as compared to controls. Conclusion: Our findings suggest that the neural disorder and behavioral deficits of anti-LGI1 encephalitis may be associated with extensive changes in brain connectivity and microstructure. These pathological alterations affect the basal ganglia and limbic system besides the temporal and frontal lobe. [ABSTRACT FROM AUTHOR]

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.

The aim of this study was to analyze the detailed characteristics of the psychiatric symptoms in patients with anti-LGI1 encephalitis. Of 16 patients, ten showed psychiatric symptoms as the initial manifestations. All 10 patients experienced mood-related symptoms. The time to immune therapy was longer in those with initial psychiatric symptoms compared to those without them. Initial manifestation of psychiatric symptoms in patients with anti-LGI1 encephalitis may be a poor prognostic factor, at least in the short term, in that it misleads both the patients and the clinicians to neglect the typically accompanied symptoms of the disease such as faciobrachial dystonic seizure, delaying the timing of immune therapy. [ABSTRACT FROM AUTHOR]

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• Seizure outcomes in a large cohort of anti-LGI1 encephalitis. • Detailed seizure semiology and EEG characteristics were described. • Seizure outcomes were associated with seizure types, age, and therapy timing. This study aimed to investigate the semiology of seizure disorders, including electroencephalographic characteristics, and seizure outcomes in participants with anti-leucine-rich glioma-inactivated 1 (LGI-1) encephalitis. Seventy participants who presented with seizures during the acute phase of anti-LGI-1 encephalitis at Peking Union Medical College Hospital from May 2013 to July 2020 were reviewed. All participants underwent follow-up for longer than 2 years. At the time of presentation, 48 (68.6%) participants had generalized seizures and 57 (81.4%) had focal seizures. The most common focal motor seizures were faciobrachial dystonic seizures (FDS). The main manifestations of focal nonmotor seizures were dyscognitive features, goosebumps, and disorders of sensation. All participants received immunomodulatory therapy. Thirty-five (50%) participants were seizure free after 1 year of follow-up, and 48 (68.6%) participants were seizure free over a follow-up of 2 years. Participants with seizures continued longer than 1 year were older than participants whose seizure duration was shorter than 1 year (P = 0.021). However, after an extended follow-up period, the difference between the incidences of seizures based on age was not significant. The frequency of focal motor seizures was higher in participants who became seizure free within 1 year, compared to participants who had seizures for longer than 1 year (75% vs 54.3%, respectively; P = 0.015). Participants with seizures continued over 2 years tended to have focal nonmotor seizures, and tended to show an elevated incidence of abnormal EEG results. Participants receiving early corticosteroid and longer duration immunosuppressant treatments, tended to have a lower risk of persistent seizures and better seizure outcomes, with no statistical significance. Most participants obtained remission from seizures after immunomodulatory therapy. The seizure manifestation of anti-LGI1 encephalitis is diverse and variable. The type of focal seizures may affect the outcome of participants with seizures. Older age could lead to longer duration of the seizure disorder, but did not affect the rate of seizures over the long term. Early and prolonged administration of immunomodulatory therapy may be useful for shortening the time to becoming seizure free. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]