LGI1-antibody Encephalitis Research Articles

Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts.

Encephalitis with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E) is a common form of autoimmune encephalitis, presenting with seizures and neuropsychiatric changes, predominantly in older males. More than 90% of patients carry the human leucocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls. Therefore, we hypothesised the presence of additional genetic predispositions. In this genome-wide association study and meta-analysis, we studied a discovery cohort of 131 French LGI1-Ab-E and a validation cohort of 126 American, British and Irish LGI1-Ab-E patients, ancestry-matched to 2613 and 2538 European controls, respectively. Outside the known major HLA signal, we found two single nucleotide polymorphisms (SNPs) at genome-wide significance (p < 5 x 10-8), implicating PTPRD, a protein tyrosine phosphatase, and LINC00670, a non-protein coding RNA gene. Meta-analysis defined four additional non-HLA loci, including the protein coding COBL gene. Polygenic risk scores with and without HLA variants proposed a contribution of non-HLA loci. In silico network analyses suggested LGI1 and PTPRD mediated interactions via the established receptors of LGI1, ADAM22 and ADAM23. Our results identify new genetic loci in LGI1-Ab-E. These findings present opportunities for mechanistic studies and offer potential markers of susceptibility, prognostics and therapeutic responses.

Characteristics and prognosis of LGI1 antibody encephalitis

Objectives: To investigate clinical manifestations and outcomes of patients with LGI1 autoimmune encephalitis. Methods: A total of 12 patients who were diagnosed with LGI1 autoimmune encephalitis were retrospectively analyzed between 2018 and 2022 at the Department of Neurology of the Affiliated Hospital of Xuzhou Medical University. Clinical characteristics, laboratory examinations, electroencephalograms, brain magnetic resonance images and prognosis were assessed. The clinical data were collected by searching through electronic medical records. Results: Among 12 patients, 8 were male and 4 were female. The average age at disease onset was 61.8 years (24–83). The most common clinical symptoms were seizures (n=10), cognitive dysfunction (n=8), and mental behavioral disorders (n=8). A total of 9 cases had hyponatremia. Brain MRI and electroencephalographic were abnormal in 7 patients each. All patients were treated with first line immunotherapy. Most patients responded well and 3 patients relapsed on follow-up. Conclusion: Characteristic features of LGI1 antibody encephalitis include subacute onset cognitive impairment, seizures, faciobrachial dystonic seizures (FBDS), and mental and behavioral abnormalities. Especially, FBDS and hyponatremia suggest LGI1-antibody encephalitis. Therefore, early identification and immunotherapy may prevent cognitive impairment and improve prognosis.

Clinical features of COVID-19-related encephalitis: comparison with the features of herpes virus encephalitis and autoimmune encephalitis

IntroductionIdentifying coronavirus disease 2019 (COVID-19)-related encephalitis without clear etiological evidence is clinically challenging. The distinctions between this condition and other prevalent encephalitis types remain unknown. Therefore, we aimed to explore the similarities and differences in the clinical characteristics of COVID-19-related encephalitis and other encephalitis types.MethodsAdult patients with encephalitis admitted to the neurology department at Xuanwu Hospital were enrolled and categorized into the following six groups based on the results of metagenomic next-generation sequencing and autoimmune antibody detection in cerebrospinal fluid (CSF): COVID-19-related encephalitis (n = 36), herpes simplex virus type 1 encephalitis (HSV-1 encephalitis; n = 28), human herpesvirus 3 encephalitis (HHV-3 encephalitis; n = 10), NMDAR-antibody encephalitis (n = 18), LGI1-antibody encephalitis (n = 12), and GABAB-antibody encephalitis (n = 8).ResultsThe predominant characteristics of COVID-19-related encephalitis include a low incidence of seizures (38.9%), cognitive defects (30.6%), and meningeal irritation signs (8.3%). Compared with HSV-1 and HHV-3 encephalitis, COVID-19-related encephalitis exhibited lower white blood cell count (2.5 count/mm3), protein (32.2 mg/dL), and immunoglobulin M, G, and A levels (0.09, 3.2, and 0.46 mg/dL, respectively) in the CSF tests. Abnormal imaging findings were present in only 36.1% of COVID-19-related encephalitis cases, mostly showing diffuse inflammation scattered in various parts, which differed from HSV-1 encephalitis. Additionally, COVID-19-related encephalitis exhibited significant differences in clinical symptoms and CSF white blood cell counts compared with NMDAR-antibody encephalitis; however, it showed limited differences compared with LGI1-antibody and GABAB-antibody encephalitis.DiscussionCOVID-19-related encephalitis and herpes virus or autoimmune encephalitis differ clinically. Symptoms and auxiliary examinations can be used as distinguishing tools.

LGI1-antibody encephalitis: how to approach this highly treatable dementia mimic in memory and mental health services.

Leucine-rich glioma-inactivated 1-antibody-encephalitis is a treatable and potentially reversible cause of cognitive and psychiatric presentations, and may mimic cognitive decline, rapidly progressive dementia and complex psychosis in older patients. This aetiology is of immediate relevance given the alternative treatment pathway required, compared with other conditions presenting with cognitive deficits.

Predictors and Clinical Characteristics of Relapses in LGI1-Antibody Encephalitis.

Relapses occur in 15%-25% of patients with leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) autoimmune encephalitis and may cause additional disability. In this study, we clinically characterized the relapses and identified factors predicting their occurrence. This is a retrospective chart review of patients with LGI1-Ab encephalitis diagnosed at our center between 2005 and 2022. Relapse was defined as worsening of previous or appearance of new symptoms after at least 3 months of clinical stabilization. Among 210 patients, 30 (14%) experienced a total of 33 relapses. The median time to first relapse was 23.9 months (range: 4.9-110.1, interquartile range [IQR]: 17.8). The CSF was inflammatory in 11/25 (44%) relapses, while LGI1-Abs were found in the serum in 16/24 (67%) and in the CSF in 12/26 (46%); brain MRI was abnormal in 16/26 (62%) relapses. Compared with the initial episode, relapses manifested less frequently with 3 or more symptoms (4/30 patients, 13% vs 28/30, 93%; p < 0.001) and had lower maximal modified Rankin scale (mRS) score (median 3, range: 2-5, IQR: 1 vs 3, range: 2-5, IQR: 0; p = 0.001). The median mRS at last follow-up after relapse (2, range: 0-4, IQR: 2) was significantly higher than after the initial episode (1, range: 0-4, IQR: 1; p = 0.005). Relapsing patients did not differ in their initial clinical and diagnostic features from 85 patients without relapse. Nevertheless, residual cognitive dysfunction after the initial episode (hazard ratio:13.8, 95% confidence interval [1.5; 129.5]; p = 0.022) and no administration of corticosteroids at the initial episode (hazard ratio: 4.8, 95% confidence interval [1.1; 21.1]; p = 0.036) were significantly associated with an increased risk of relapse. Relapses may occur years after the initial encephalitis episode and are usually milder but cause additional disability. Corticosteroid treatment reduces the risk of future relapses, while patients with residual cognitive dysfunction after the initial episode have an increased relapse risk.

Corticospinal tract hyperintensity in patients with LGI1-antibody encephalitis and other central nervous system disorders with neuroglial antibodies

The frequency of corticospinal tract (CST) T2/FLAIR hyperintensity in disorders with neuroglial antibodies is unclear. Herein, we retrospectively reviewed brain MRIs of 101 LGI1-antibody encephalitis patients, and observed CST hyperintensity in 30/101 (30%). It was mostly bilateral (93%), not associated with upper motor neuron signs/symptoms (7%), and frequently decreased over time (39%). In a systematic review including patients with other neuroglial antibodies, CST hyperintensity was reported in 110 with neuromyelitis optica (94%), myelin oligodendrocyte glycoprotein-associated disease (2%), Ma2-antibody (3%) and GAD65-antibody paraneoplastic neurological syndrome (1%). CST hyperintensity is not an infrequent finding in LGI1-Ab encephalitis and other disorders with neuroglial antibodies.

Magnetic Resonance Imaging Characteristics of LGI1-Antibody and CASPR2-Antibody Encephalitis

Rapid and accurate diagnosis of autoimmune encephalitis encourages prompt initiation of immunotherapy toward improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis, and awaiting autoantibody results can delay immunotherapy. To identify simple magnetic resonance imaging (MRI) characteristics that accurately distinguish 2 common forms of autoimmune encephalitis, LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD). This cross-sectional study involved a retrospective, blinded analysis of the first available brain MRIs (taken 2000-2022) from 192 patients at Oxford University Hospitals in the UK and Mayo Clinic in the US. These patients had LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings were validated in an independent cohort by 3 neurologists (n = 105). Groups were statistically compared with contingency tables. Data were analyzed in 2023. MRI findings including T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensities, swelling or volume loss, presence of gadolinium contrast enhancement, and diffusion-weighted imaging changes. Correlations with clinical features. Among 192 participants with MRIs reviewed, 71 were female (37%) and 121 were male (63%); the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and/or FLAIR hyperintensities were less likely to extend outside the temporal lobe (3/42 patients [7%] vs 17/18 patients [94%] with VE; P < .001, and 3/4 patients [75%] with CJD; P = .005), less frequently exhibited swelling (12/55 [22%] with LGI1/CASPR2-Ab-E vs 13/22 [59%] with VE; P = .003), and showed no diffusion restriction (0 patients vs 16/22 [73%] with VE and 8/10 [80%] with CJD; both P < .001) and rare contrast enhancement (1/20 [5%] vs 7/17 [41%] with VE; P = .01). These findings were validated in an independent cohort and generated an area under the curve of 0.97, sensitivity of 90%, and specificity of 95% among cases with T2/FLAIR hyperintensity in the hippocampus and/or amygdala. In this study, T2 and/or FLAIR hyperintensities confined to the temporal lobes, without diffusion restriction or contrast enhancement, robustly distinguished LGI1/CASPR2-Ab-E from key differential diagnoses. These observations should assist clinical decision-making toward expediting immunotherapy. Their generalizability to other forms of autoimmune encephalitis and VE should be examined in future studies.

Efficacy of immunotherapy and prognosis in anti-LGI1 encephalitis patients: A meta-analysis.

To assess the efficacy and safety of immunotherapy for LGI1 antibody encephalitis, and consider the predictors of poor outcomes following immunotherapy. We searched PubMed and Embase for articles reporting the immunotherapy data of anti-LGI1 encephalitis patients. The proportions of patients with poor outcomes (modified Rankin Scale [mRS] score > 2) at 3 months, 12 months, and the last follow-up, as well as the odds ratio [OR] of predictors were pooled. The review included 162 articles with 1066 patients. The proportion of patients with poor functional outcomes was 21% at 3 months, 14% at 12 months, and 14% at the last follow-up after receiving immunotherapy. The proportion of patients with reported relapse was 16.6%. The mean duration from onset to the first relapse was 15.6 months. Predictors significantly associated with poor outcomes were age (increase of 1 year), the presence of cognitive impairment, and CSF LGI1 antibody positive. We did not find a statistically significant association between the worst mRS score in the acute phase, the presence of faciobrachial dystonic seizures (FBDS), days from symptom onset to immunotherapy, second-line treatment, maintenance immunotherapy, or follow-up time and outcomes. Although most patients respond to immunotherapy, a minority of patients still have poor outcomes. Advanced age, cognitive impairment, and CSF LGI1 antibody positive are associated with an increased risk of poor outcomes. However, due to the insufficiency of the data, these conclusions need to be interpreted with caution.

Cortical metabolic characteristics of anti-leucine-rich glioma-inactivated 1 antibody encephalitis based on 18F-FDG PET.

A general glucose metabolism pattern is observed in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis; however, it is unclear whether further subregional metabolic differences exist. Therefore, the present study aimed to conduct an in-depth exploration of the features of glucose metabolism within specific brain areas using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). This retrospective study enrolled thirteen patients confirmed with LGI1 antibody encephalitis who were admitted to Beijing Tiantan Hospital from June 2021 to September 2022. All patients underwent 18F-FDG PET before initiating clinical treatment. Changes in glucose metabolism in specific brain areas were analyzed using Cortex ID software. The laterality of 18F-FDG uptake was assessed, and differences in specific brain areas were compared using paired t-tests. Significant metabolic changes in at least one brain region in 11 out of 13 patients (84.6%) were revealed by semi-quantitative analysis (z-score > 2). A bilateral decrease in the 18F-FDG metabolic pattern was revealed in almost all brain regions of interest; in contrast, a hypermetabolic pattern was observed in the medial temporal region, with mean z-scores of 1.75 ± 3.27 and 2.36 ± 5.90 on the left and right sides, respectively (p = 0.497). In the prefrontal and temporal lobes, 18F-FDG metabolism was significantly lower in the lateral region than in the medial region on both sides. For the cingulate cortex, significant hypometabolism was also observed in the posterior part compared to the anterior counterpart on both the left (z-score: -1.20 ± 1.93 vs. -0.42 ± 1.18, respectively; p = 0.047) and right (z-score: -1.56 ± 1.96 vs. -0.33 ± 1.63, respectively; p = 0.001) sides. However, a significant difference in regional metabolism was observed only on the left side (p = 0.041). An asymmetric 18F-FDG metabolic pattern exists in patients with anti-LGI1 encephalitis. Meanwhile, varied regional metabolic differences were revealed bilaterally in specific cerebral areas, which could be associated with the clinical manifestations.

Clinical Improvement Following Delayed Initiation of Immunotherapy in a Case of LGI1 Antibody Encephalitis Presenting with Faciobrachial Dystonic Seizures Following COVID-19 Vaccination

Objective To demonstrate a case of suspected post-vaccine autoimmune encephalitis associated with leucine-rich glioma-inactivated protein (LGI1) antibodies with significant clinical improvement after initiation of immunotherapy nearly a year after symptom onset. Background Although the autoimmune encephalitides have overlap in presentation, some have unique manifestations (such as orofacial dyskinesias seen with NMDA encephalitis). These unique associations can serve as a clinical marker of response to treatment and even allow for earlier initiation of immunotherapy while awaiting results from antibody testing. LGI1 encephalitis characteristically presents with faciobrachial dystonic seizures (FBDS) that are refractory to anti-seizure medications (ASMs) but responsive to immunotherapy. Design/Methods Case report Results A previously healthy and highly independent 89-year-old woman developed what she described as abnormal posturing and spasms of the right shoulder two to three weeks after receiving the J&amp;J COVID-19 vaccine. The abnormal movements progressed to involve the right side of her face and were refractory to multiple ASMs. EEG captured multiple events without epileptiform correlate. Several months later she developed paranoia, delusions, and hallucinations. Autoimmune encephalopathy panel returned positive for the LGI1-antibody around nine months after the onset of FBDS. Upon our initial exam, she had a fluctuating level of arousal, impaired recall of recent events, and was tangential in conversation. There were frequent, brief, repetitive, dystonic movements of the right side of the face consistent with FBDS. Admission was arranged for immunotherapy (intravenous methylprednisolone and intravenous immunoglobulin). Upon follow-up four weeks later, there was significant improvement in arousal and concentration with resolution of FBDS and delusions. Conclusions This case highlights a classic case of LGI1 encephalitis after vaccination presenting with FBDS and progressive cognitive changes. Despite immunotherapy being delayed, there was marked clinical improvement. It is important to recognize this entity and that it typically has a favorable outcome.

Seizure underreporting in LGI1 and CASPR2 antibody encephalitis.

Patients with anti-leucine-rich glioma-inactivated 1 protein (LGI1) or anti-contactin-associated protein 2 (CASPR2) antibody encephalitis typically present with frequent epileptic seizures. The seizures generally respond well to immunosuppressive therapy, and the long-term seizure outcome seems to be favorable. Consequentially, diagnosing acute symptomatic seizures secondary to autoimmune encephalitis instead of autoimmune epilepsy was proposed. However, published data on long-term seizure outcomes in CASPR2 and LGI1 antibody encephalitis are mostly based on patient reports, and seizure underreporting is a recognized issue. Clinical records from our tertiary epilepsy center were screened retrospectively for patients with LGI1 and CASPR2 antibody encephalitis who reported seizure freedom for at least 3 months and received video-electroencephalography (EEG) for >24 h at follow-up visits. Twenty (LGI1, n=15; CASPR2, n=5) of 32 patients with LGI1 (n=24) and CASPR2 (n=8) antibody encephalitis fulfilled these criteria. We recorded focal aware and impaired awareness seizures in four of these patients (20%) with reported seizure-free intervals ranging from 3 to 27 months. Our results question the favorable seizure outcome in patients with CASPR2 and LGI1 antibody encephalitis and suggest that the proportion of patients who have persistent seizures may be greater. Our findings underline the importance of prolonged video-EEG telemetry in this population.

Evaluation of LGI1-antibody Encephalitis, a Rare Cause of Limbic Encephalitis, from Diagnosis to Treatment

Evaluation of LGI1-antibody Encephalitis, a Rare Cause of Limbic Encephalitis, from Diagnosis to Treatment

LGI1-Antibody Associated Autoimmune Encephalitis Complicated by Primary Polydipsia.

LGI1-Antibody Associated Autoimmune Encephalitis Complicated by Primary Polydipsia.

Clinical Course and Features of Seizures Associated With LGI1-Antibody Encephalitis

To determine risk factors associated with clinical relapses and development of chronic epilepsy in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) immunoglobulin G encephalitis. Patients with seizures related to LGI1-antibody encephalitis with ≥24 months of follow-up from disease onset were identified in the Mayo Clinic electronic medical record and neuroimmunology laboratory records. Charts were reviewed to determine clinical factors, seizure types, imaging, treatment, occurrence of relapse, and outcome. Binary logistic regression analysis was performed to identify predictors of the development of chronic epilepsy. Univariate Cox proportional hazards regression was used to examine the influence of baseline characteristics on relapse risk. Forty-nine patients with LGI1-antibody encephalitis and acute symptomatic seizures were identified. Almost all patients (n = 48, 98%) were treated with immunotherapy. Eight had definite and 2 had possible chronic epilepsy at the last follow-up (10 of 49, 20.4%). Female sex (p = 0.048) and younger age at disease onset (p = 0.02) were associated with development of chronic epilepsy. Relapses occurred in 20 (40.8%), with a median time to first relapse of 7.5 months (range 3-94 months). Initial treatment with long-term steroid-sparing immunotherapy was associated with reduced risk of relapse (hazard ratio 0.28, 95% confidence interval 0.11-0.73, p = 0.009). Chronic epilepsy occurred in 20.4% of our patients with LGI1-antibody encephalitis despite aggressive immunotherapy. Risk factors for chronic epilepsy were female sex and earlier age at onset. Relapses occurred in 40.8% of patients with prolonged follow-up, and long-term steroid-sparing immunotherapy was associated with a lower relapse rate.

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

BackgroundLeucine-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 presentationIn 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.ConclusionTo 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.

Asymmetrical manifestation of faciobrachial dystonic seizures in leucine‐rich, glioma‐inactivated 1 antibody encephalitis: A case report

AbstractBackgroundLeucine‐rich, glioma‐inactivated (LGI1) antibody encephalitis is a rare autoimmune encephalitis characterized by faciobrachial dystonic seizures (FBDS), temporal lobe epilepsy, prominent short‐term memory deficits and altered mental status. FBDS are very brief, frequent stereotypical dystonic seizures of the ipsilateral face, arms and legs. FBDS are often initially unilateral and evolve bilaterally or asynchronously.Case presentationA 49‐year‐old woman developed frequent FBDS of her right side. Fluid attenuated inversion recovery imaging showed hyperintense lesions in the right striatum. She was treated with only anti‐epileptic agents. FBDS emerged on her left side soon after cessation of FBDS on her right side. LGI1 antibody was positive in the serum and cerebrospinal fluid. Steroid therapy was added on day 157, and thereafter, FBDS subsided completely, although cognitive impairment remained.ConclusionsA case of LGI1 antibody encephalitis with asymmetrical manifestation of FBDS after resolution of the first unilateral symptoms was described. This case suggests that LGI1 antibody encephalitis can affect each side of the brain asymmetrically and asynchronously.

Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors.

Paraneoplastic neurological syndromes (PNSs) are rare complications of systemic cancers that can affect all parts of the central and/or peripheral nervous system. A body of experimental and clinical data has demonstrated that the pathogenesis of PNSs is immune-mediated. Nevertheless, the mechanisms leading to immune tolerance breakdown in these conditions remain to be elucidated. Despite their rarity, PNSs offer a unique perspective to understand the complex interplay between cancer immunity, effect of immune checkpoint inhibitors (ICIs), and mechanisms underlying the attack of neurons in antibody-mediated neurological disorders, with potentially relevant therapeutic implications. In particular, it is reported that ICI treatment can unleash PNSs and that the immunopathological features of PNS-related tumors are distinctive, showing prominent tumor-infiltrating lymphocytes and germinal center reactions. Intriguingly, similar pathological substrates have gained further attention as potential biomarkers of ICI-sensitivity and oncological prognosis. Moreover, the genetic analysis of PNS-associated tumors has revealed specific molecular signatures and mutations in genes encoding onconeural proteins, leading to the production of highly immunogenic neoantigens. Other than PNSs, autoimmune encephalitides (AEs) comprise a recently described group of disorders characterized by prominent neuropsychiatric symptoms, diverse antibody spectrum, and less tight association with cancer. Other triggering factors seem to be involved in AEs. Recent data have shed light on the importance of preceding infections (in particular, herpes simplex virus encephalitis) in inducing neurological autoimmune disorders in susceptible individuals (those with a selective deficiency in the innate immune system). In addition, in some AEs (e.g. LGI1-antibody encephalitis) an association with specific host-related factors [e.g., human leukocyte antigen (HLA)] was clearly demonstrated. We provide herein a comprehensive review of the most recent findings in the field of PNSs and AEs, with particular focus on their triggering factors and immunopathogenesis.

Clinical and electrographic characteristics of seizures in LGI1-antibody encephalitis

PurposeThe purpose of this study was to analyze the clinical and electrographic characteristics of seizures in LGI1-antibody encephalitis. MethodsThe methods utilized in this study were prospective analysis of the clinical manifestations, types of seizures, electroencephalogram (EEG), adjuvant examination, treatment and prognosis of 19 cases of LGI1-antibody encephalitis diagnosed from January 2017 to February 2018 in First Affiliated Hospital of Zhengzhou University, and reviewed related literatures. ResultsThe 15/19 (79%) patients were male, and the average onset age was 58 years (23–82). The following cases were observed: 17 (89%) with epilepsy seizures, 14 (73%) with mental disorders, and 13 (68%) with cognitive impairment. Types of epilepsy were including focal aware seizures, focal-impaired awareness seizures, focal to bilateral tonic–clonic seizures, and status epilepticus. The motor events were most commonly clonus or automatisms, and the sensory events were frequently body shuddering. The 13 patients had faciobrachial dystonic seizures (FBDS); the median frequency was 48 per day (range 5–180). In some video-EEGs, multifocal ictal epileptiform discharges from frontal, temporal, and apical regions, and interictal slow wave activity were observed in patients. Normal EEG appeared in all patients during FBDS. Five patients had hyponatremia, and brain magnetic resonance imaging (MRI) results of 5 cases were abnormal. All patients were treated with antiepileptic drugs and immunotherapy, and their clinical symptoms were improved. During the follow-up period, 13 patients recovered basically, and 6 patients relapsed. One patient died of status epilepticus after relapse. ConclusionsFaciobrachial dystonic seizure and various types of epileptic seizures are characteristic manifestations of LGI1-antibody encephalitis, which can assist in early diagnosis. Once this has been diagnosed, antiepileptic drugs and immunotherapy should be given as soon as possible to the patient.

LGI1 expression and human brain asymmetry: insights from patients with LGI1-antibody encephalitis

BackgroundWhile brain asymmetry has been a fascinating issue in neuroscience, the critical mechanism remains to be elucidated. Based on some index cases with asymmetric 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) uptake in leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis, we hypothesized LGI1 expression could be asymmetrically distributed in the human brain.MethodsWe enrolled 13 patients who were diagnosed with LGI1-antibody encephalitis between June 2012 and January 2018 at Seoul National University Hospital. Their pretreatment 18F-FDG-PET images were analyzed to find asymmetry between the left and right hemispheres. Guided by these observations, expression of LGI1 in the human hippocampus and the globus pallidus of both cerebral hemispheres was studied in nine post-mortem human brains.ResultsEleven of the 13 LGI1-antibody encephalitis patients (84.6%) showed asymmetrical FDG high uptake in the hippocampus: nine (81.8%) on the left hippocampus and two (18.2%) on the right. In the basal ganglia, seven patients (53.8%) showed asymmetry: four (57.1%) on the left and three (42.9%) on the right. The asymmetry was not evident in the laterality of faciobrachial dystonic seizures, brain MRI, and EEG. When the expression of LGI1 protein was analyzed in nine post-mortem human brains by western blotting, LGI1 expression was higher on eight left globus pallidus samples (88.89%, P = 0.019) and on four left hippocampal samples (44.44%, P = 0.652), compared to their right hemisphere samples.ConclusionsImaging parameters from patients with LGI1-antibody encephalitis and studies of LGI1 protein expression suggest that LGI1 is asymmetrically distributed in the human brain. These observations have implications for our understanding of human brain development.

CMV Colitis: A rare complication in a LGI-1 antibody encephalitis patient treated with Cellcept (P6.112)

CMV Colitis: A rare complication in a LGI-1 antibody encephalitis patient treated with Cellcept (P6.112)