anti-GABAB Receptor Encephalitis Research Articles

Anti-GABAB receptor encephalitis: clinical and laboratory characteristics, imaging, treatments and prognosis.

Anti-GABABR encephalitis is a rare disease reported to be often associated with tumors. The current study aims to summarize the clinical characteristics, imaging features, treatments, outcomes and explore the potential prognosis risk factors of patients with anti-GABABR encephalitis. Patients tested positive for anti-GABABR were retrospective studied from a single medical center in China over a period of 3 years. They were followed up for a maximum period of 18 months. Clinical data were summarized and prognostic factors including demographic characteristics, laboratory tests, and neurological functions were compared between survived and deceased patients at 18 months follow-up. Twenty-six patients, 10 females (38.5%) and 16 males (61.5%), diagnosed with anti-GABABR encephalitis were studied. The median age was 58 years. Of the 23 cases with complete clinical data, their main manifestations were epileptic seizures (65%), mental and behavioral abnormalities (52%), and cognitive impairment (48%). 7 (30.4%) cases had tumors: 5 small cell lung cancer (SCLC), 1 rectum adenocarcinoma (moderately differentiated) and 1 esophageal squamous cell carcinoma. MRI showed 5 (22%) cases had T2 FLAIR increased signals in cortex but with different regions affected. One of the two patients scanned for PET-CT showed hypermetabolism in the left temporal lobe region. The disease course ranged from 5 days to 3 years. 2 patients (one had esophageal carcinoma) without immunotherapy and 3 patients (one had SCLC) that did not response to immunotherapy died soon after diagnosis. 18 patients improved after immunotherapy while 3 (all had SCLC) died after relapses. The prevalence of epileptic seizures and malignancies was significantly lower in the survival group than in the deceased group at 18-months follow-up, the same as the admission mRs score. Serum fibrinogen, cerebrospinal fluid immunoglobulin G quotient, and 24-hour intrathecal synthesis rate were significantly lower in the survival groups as well. Cortex T2 FLAIR abnormalities were only observed in a small proportion of anti-GABABR encephalitis patients with heterogeneous MRI phenotypes. High mRS score at admission, epileptic seizures and the presence of a tumor indicated a poor prognosis, while the underlying mechanism of the later two factors should be investigated further.

Cytokines/chemokines and soluble immune checkpoint molecules in anti-GABAB receptor encephalitis

Anti-gamma-aminobutyric-acid B receptor (anti-GABABR) encephalitis is a rare form of autoimmune limbic encephalitis (ALE) that is closely associated with tumor comorbidity. The purpose of this study is to identify the expressive pattern of cytokines/ chemokines and soluble immune checkpoint molecules (sICMs) in anti-GABABR encephalitis in order to evaluate the clinical condition and provide new treatment options. A total of 40 cytokines/chemokines and 10 sICMs in the serum of 10 patients with anti-GABABR encephalitis and eight controls were measured. The differentially expressed cytokines/chemokines and sICMs were selected to explore the correlations with disease prognosis, CSF routine and antibody titers. Eight cytokines/chemokines were found to be more abundant in patients than in healthy donors (HDs), while 14 were found to be less abundant in patients. In terms of sICMs, patients' serum contained higher level of soluble ICOS and ICOSL but lower level of soluble CD86. Unfavorable prognosis was associated with high serum level of PDGFB, IL-17A, and soluble ICOSL but not with low levels of IL-4. Increased levels of IL-17A, CCL15, and soluble ICOS were found frequently in the patients with CSF-exclusive OCBs, while soluble ICOSL and CCL24 expression was lower in these patients. High levels of IL-1 F2 and TCA-3 were correlated with the presence of tumors in patients. The majority of patients with anti- GABABR encephalitis had an unfavorable prognosis in one year of follow-up. Serum PDGFB, IL-17A, IL-4 and soluble ICOSL level were associated with the poor clinical outcomes in one-year follow up.

Anti-GABAB receptor encephalitis after COVID-19 infection.

Anti-GABAB receptor encephalitis after COVID-19 infection.

Case Analysis and Literature Review of Thirteen Patients with Autoimmune Encephalitis.

Objective To investigate the clinical manifestations, laboratory and imaging examinations, and the treatment outcomes of autoimmune encephalitis (AE). Methods The clinical data of 13 patients with autoimmune encephalitis who were hospitalized in the department of neurology, Liaocheng People's Hospital from July 2016 to August 2018 were retrospectively analyzed. Results The average age of onset of the 13 patients was 45 years, including 6 cases (46%) of anti-NMDAR encephalitis, 3 cases (23%) of anti-GABAB receptor encephalitis, and 4 cases (30%) of anti-LG11 encephalitis, and 4 of them showed abnormal signals of brain MRI (30%). 13 patients (100%) had cognitive impairment and psychiatric symptoms; seizures occurred in 12 patients (92%); lung cancer was found in 1 patient (7%). One case was given up because of the treatment of lung cancer, the other was controlled obviously in epilepsy, and cognitive impairment and abnormal mental behavior were also significantly improved. Conclusion Patients with AE still need to be diagnosed early to avoid missed diagnosis and receive early immunosuppressive therapy, which could effectively reduce mortality and morbidity. A detailed history, clinical manifestations, and positive results for specific NSAbs tests can confirm the diagnosis, and the treatment is mainly done by immunosuppressive therapy.

Paediatric anti-GABAB receptor encephalitis associated with SARS-CoV-2 (COVID-19) infection

Though we are approaching the end of second wave of COVID pandemic, we are still unrevealing the various presentation this viral infection can result in. There are few cases reported to have anti NMDA autoimmune encephalitis associated with COVID-19 infection or MIS-C. Here we are reporting one of its variants that was anti-GABAB receptor encephalitis associated with COVID-19 infection. We are reporting a 9 years old female child who was a known case of seizure disorder and on regular medications presented on 4th day of RT-PCR positive status for COVID-19 with complains of convulsions which was managed with antiepileptics. On day 6 of hospitalization she had autonomic instability in the form of tachyarrhythmia, repitation of speech, sudden outburst of laughter and on day 7 child landed in status epilepticus. Autoimmune encephalitis suspected secondary to COVID-19 infection and the child was started on IVIG but not much of improvement seen with this. CSF analysis showed weakly positive anti GABAB antibodies and child had persistently elevated inflammatory markers hence started on high dose corticosteroid. MIS-C ruled out. Child showed drastic improvement both clinical and biochemical after high dose corticosteroids. Prompt treatment with IVIG/corticosteroids have shown a drastic improvement in our child just like in any other autoimmune encephalitis. Though further detailed study is required to prove its exact mechanism in COVID-19 infection, it should be thought of when appropriate and prompt early initiation of therapy will help us reduce morbidity and mortality associated with it.

Anti-GABAB receptor encephalitis associated with combined small cell lung carcinoma

Autoimmune encephalitis with antibodies against the gamma-aminobutyric acid-B receptor is a relatively rare disease. We report a case with characteristic symptoms of limbic encephalitis associated with combined small cell lung carcinoma. The brain magnetic resonance imaging showed bilateral temporal lesions and the photoemission tomography revealed regional heterogenous metabolism across the brain. The double labeling of anti-gamma-aminobutyric acid-B receptor autoantibodies both in the tissues of neuroendocrine and small cell neoplasia was a unique feature of this patient.

Anti-GABAB Receptor Encephalitis Presenting with Atypical Corticobasal Syndrome in a Patient with Parkinson's Disease.

Anti-GABAB Receptor Encephalitis Presenting with Atypical Corticobasal Syndrome in a Patient with Parkinson's Disease.

Clinical characteristics and long-term follow-up of seven cases of anti-GABABR encephalitis in patients of Han Chinese descent

ObjectiveTo improve the diagnosis and treatment of anti-GABAB receptor (anti-GABABR) encephalitis and prevent misdiagnosis or non-diagnosis.MethodsWe retrospectively examined the chief clinical manifestations, auxiliary examination results, treatment strategies, treatment efficacy, and long-term follow-up results of seven consecutive patients with anti-GABABR encephalitis.ResultsEpileptic seizures were the first symptom in 100% of the patients; 85.7% had memory deficit in the hospital, 42.8% had residual symptoms of cognitive impairment at discharge, and 28.6% had cognitive impairment at the end of follow-up; 71.4% of the patients had psychosis in the hospital, 57.1% had residual symptoms of psychosis at discharge, and 14.3% still had psychosis at the end of follow-up. However, the clinical symptoms (psychiatric disorders, cognitive decline) and signs (consciousness disturbance) at onset and after follow-up were not significantly different (P > 0.05). In 71.4% of the patients, anti-GABABR antibody serum levels were higher than those in the cerebrospinal fluid (especially in patients with lung cancer). Magnetic resonance imaging in 71.4% of patients indicated that the marginal lobe demonstrated encephalitis lesions. The average modified Rankin Scale score (2.0 ± 2.31) at follow-up was significantly better than that (3.86 ± 0.90) at the time of admission (P < 0.05).ConclusionThe clinical characteristics of anti-GABABR encephalitis were refractory epilepsy, psychiatric disorders, and cognitive impairment. Multiple antiepileptic drugs are crucial for the treatment of intractable epilepsy. Clinicians should eliminate the possibility of small-cell lung cancer in patients with high anti-GABABR antibody levels. Early active immunotherapy is effective, and the long-term prognosis is good for patients without tumors.

Clinical features and long-term outcomes of seizures associated with autoimmune encephalitis: A follow-up study in East China

PurposeTo evaluate the clinical characteristics, treatment outcomes, prognosis and potential risk factors of patients in East China with seizure secondary to autoimmune encephalitis. MethodsFrom February 2014 to June 2016, 113 patients diagnosed with autoimmune encephalitis in Huashan Hospital, Fudan University, were enrolled in our study. After at least two years of follow-up, we retrospectively analyzed the patients’ clinical details, electroencephalograph performance, brain MRI findings, and the therapeutic outcome. Patients underwent clinical evaluation every 3 months. We compared the clinical characteristics and epileptic prognosis of autoimmune encephalitis per antibody type. The association of the epileptic prognosis and EEG abnormalities was evaluated. GTE (Grand Total EEG) Score was used to evaluate EEG abnormalities. Statistic methods included ANOVA, Bonferroni correction test. ResultsTreatment outcomes were assessabled in 103 patients (10 patients died or withdrew), including anti-GABABR encephalitis (11), anti-LGI1 encephalitis (16), anti-NMDAR encephalitis (73), Caspr2 antibody encephalitis (3). 83 patients had seizures, who underwent both immunotherapy and anti-epileptic drugs therapy. In terms of seizure type, 57 (68.7%) patients exhibited focal to bilateral tonic-clonic seizure (FBTCS), 51 (61.4%) patients exhibited focal-impaired awareness seizure (FIAS) or focal aware seizure (FAS). 18 (21.7%) patients developed to status epilepticus. 30 (36%) patients had multiple types of seizures. 39 (47%) patients had daily seizures. 80.7% (67/83) of patients with epilepsy had seizure remission. During the 24 months of follow-up, 11 (11%) patients had clinical relapses. GTE scores were significantly different between the group with seizure reduction < 75% and the group with seizure remission (p = 0.009). Imaging abnormalities existed in 53% of the patients in our cohort, but lacked specificity during the acute phase. ConclusionAutoimmune encephalitis (AE) presents with large seizure burden with differing seizure semiology among different antibody types. Except for anti-GABAb receptor encephalitis, it may not be necessary for other AE types to apply long-term use of anti-epileptic drugs (AEDs). The GTE Score can be used to evaluate the EEG abnormalities and may be a predictor of seizure outcomes. MRI findings during the acute phase are non-specific. Long-term follow-up MRIs may be much more meaningful in evaluating prognosis.

Isolated seizures are a common early feature of paraneoplastic anti-GABAB receptor encephalitis.

To report the clinical features and long-term outcome of 22 newly diagnosed paraneoplastic patients with GABAB receptor antibodies (GABABR-Abs). Retrospective clinical study of CSF-confirmed cases of GABABR-Abs encephalitis. We identified 22 patients (4 female) with GABABR-Abs, with a median age of 64years (range 55-85). All were paraneoplastic: 20 small-cell lung cancer, one malignant thymoma, and one uncharacterized lung mass. The most frequent first symptom was the isolated recurrent seizures without cognitive inter-ictal impairment in 17 patients (77%). In the other, three presented the first behavioral disorders and two presented de novo status epilepticus (SE). After a median delay of 10days (range 1-30), the recurrent seizures' phase was followed by an encephalitic phase characterized by confusion in 100% of cases and SE in 81% (n = 17), with 53% (n = 9) non-convulsive SE. Dysautonomic episodes were frequent (36%, n = 8, bradycardia and central apnea) and killed three patients. CSF study was abnormal in 95% of the cases (n = 21). At the encephalitic phase, MRI showed a temporal FLAIR hypersignal in 73% (n = 16) of the cases. First-line immunotherapy was initiated after a median delay of 26days (range 6-65) from disease onset, and a partial response was observed in 10 out of 20 patients (50%). There was no complete response. Two years after onset, a massive anterograde amnesia affected all still alive patients. Nine patients died from cancer progression (median survival: 1.2years). Paraneoplastic GABABR-Abs encephalitis is characterized by a stereotype presentation with an epilepsy phase before an encephalitic phase with dysautonomia. The functional prognosis is poor.

The gamma-aminobutyric acid-B receptor (GABAB) encephalitis: clinical manifestations and response to immunotherapy

ABSTRACTPurpose: We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyze the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes.Methods: Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated.Results: Of the 11 patients, seven were males, and a mean age at presentation of 63 years (range: 47–79 years). The major clinical features include cognitive decline (9/11), epilepsy (10/11), mental and behavioral disorders (6/11), involuntary movement (4/11), sleep disorders (2/11), hearing loss (1/11), disturbance of consciousness (4/11) and fever (3/11). GABA-B receptor antibody was positive in serum and/or cerebrospinal fluid in 11 patients. Small-cell lung cancer was detected in five patients. Electroencephalogram monitoring demonstrated abnormal discharge in 10 cases. Epileptiform activities were found in five patients. Four patients showed abnormality in hippocampal region, parahippocampal gyrus, temporal and occipital lobe on magnetic resonance imaging. Ten patients accepted first-line immune therapy. Five patients with small-cell lung cancer received oncologic treatment. During a median follow-up of 11 months, eight patients showed a good outcome, two patients (cases 8 and 9) with tumors had a poor one and one patient (case 10) died of status epilepticus.Conclusion: Anti-GABAB receptor encephalitis is an uncommon autoimmune disease, which has been known to be often associated with cancer. Generally, patients associated with GABABR GABA-B receptor antibody encephalitis respond well to immunotherapy, especially if started early.

The Elephant in the Room: GABAB Receptor Autoantibody-Associated Paraneoplastic Neurological Syndrome Masquerading as Small Cell Lung Cancer

SESSION TITLE: Lung Cancer 3 SESSION TYPE: Affiliate Case Report Slide PRESENTED ON: Wednesday, November 1, 2017 at 11:00 AM - 12:15 PM INTRODUCTION: Paraneoplastic neurological syndrome (PNS) is rare in daily clinical practice, and may be the heralding sign of malignancy. Early recognition can lead to prompt diagnosis and potential reversal of neurologic manifestations with treatment of the underlying cancer. We describe a woman who initially presented with Limbic Encephalitis (LE) and was subsequently diagnosed with small cell lung cancer (SCLC). CASE PRESENTATION: A 64-year-old woman with an 80-pack-year smoking history presented with acute onset seizures, confusion, and memory loss. On physical exam, she was oriented to person only. CT Head demonstrated encephalomalacia of the right temporal and frontal lobe, and an MRI brain confirmed the same. An EEG showed continuous diffuse mixed theta and alpha slowing of the background suggestive of mild diffuse cerebral dysfunction. A lumbar puncture was performed demonstrating 6 WBC (85% lymphocytes), 49 protein, 61 glucose. CSF studies were negative for cytology, VDRL, EBV, and HSV. Autoimmune serologies were also negative, but CSF subsequently returned positive for GABAB receptor autoantibody (GABAB R Ab). PET CT (Fig.1) showed increased FDG uptake in enlarged left hilar and subcarinal lymph nodes, without a primary lung mass. An EBUS-TBNA of the hilar lymph node confirmed SCLC. (Fig.2) DISCUSSION: GABAB R Ab resulting in paraneoplastic LE is a relatively recent clinical entity first described in 20111. In a group of 3989 patients with suspected autoimmune encephalopathy, the incidence of GABAB R Ab was 0.2%1. Most of these patients had SCLC and showed improvement of neurologic symptoms with treatment. Most recently, a case series of patients with anti-GABAB R Ab LE emphasized the typical triad of clinical presentation, including memory alteration, seizures, and SCLC2. CONCLUSIONS: Although a rare clinical entity, GABAB R Ab is closely associated with LE and SCLC. The misdiagnosis rate of anti-GABAB receptor encephalitis is high as testing is not always readily available. GABAB R Ab LE with concomitant SCLC is associated with a median survival of less than one year. The diagnosis requires strong clinical suspicion, and prompt treatment for improved outcomes. Reference #1: Jefferey et al. GABAB receptor autoantibody frequency in service serologic evaluation. Neurology 2013. 81;882-7. Reference #2: Liu KQ, Yan SQ, Lou M. Gamma-aminobutyric-acid-B receptor antibodies in limbic encephalitis with small cell lung cancer. Neuroimmunol Neuroinflammation 2015;2(3):187-9. DISCLOSURE: The following authors have nothing to disclose: Nikita Desai, Marina Mosunjac, Munish Luthra No Product/Research Disclosure Information

Anti-gamma-aminobutyric acid B receptor encephalitis: 2 cases report and literatures review

Objective To discuss the characteristics of clinical features, diagnosis and therapy procedure of Anti-gamma-aminobutyric acid B(anti-GABAB)receptor encephalitis. Methods Procedure of clinical diagnosis and treatment in two patients with anti-GABAB receptor encephalitis were retrospected in Neurological Department of Tianjin Huanhu Hospital and the characteristics of anti-GABAB receptor encephalitis were analyzed with literature review. Results In both patients, the clinical manifestations were epileptic seizure, which was a focal seizure at first, seconded by generalized tonic clonic seizure, with frequent attacks or epilepticus state.Significant cognitive and memory impairments and psychological and behavioral abnormalities were observed during the course of the disease.Abnormal MRI signals were found in mesial temporal lobe, with normal electroencephalography.Antibody against anti-GABABreceptor was positive in both cerebrospinal fluid and blood, and immune regulation therapy was effective. Conclusions The patients present with epileptic seizures, seconded by cognitive and memory impairment, often accompanied by MR imaging-revealed mesial temporal lobe lesion.And positive anti-GABAB receptor antibody is major characteristics of anti-GABAB receptor encephalitis.The patients often combine small cell lung cancer, and Immune regulation therapy is effective. Key words: Receptor GABAB; Encephalitis

Anti-GABAB receptor encephalitis: clinical analysis of 5 cases

Objective To investigate the clinical manifestation, auxiliary examination characteristics, therapeutic intervention and prognosis of anti-GABAB receptor encephalitis. Methods Clinical data of 5 patients diagnosed as anti-GABAB receptor encephalitis in Neurology Department of Zhengzhou University People′s Hospital were retrospectively analyzed. Results The initial symptom was seizures in all of the 5 patients with anti-GABAB receptor encephalitis. During the course of disease, mental and behavior disorders were found in 4 patients, cognitive disorder in 3 patients, autonomic dysfunction in 1 patient, central hypoventilation and parasomnia in 1 patient. Brain MRI showed limbic system lesions in 3 patients. Cerebrospinal fluid (CSF) test indicated lymphocytosis in three patients. The anti-GABABR antibody was positive in both serum and CSF in all patients. Chest CT showed lung occupying lesions in 4 patients, of which 2 lesions were diagnosed as small cell lung cancer by pathological examination. All patients received immunotherapy after being diagnosed as anti-GABAB receptor encephalitis and responded well to immunotherapy. 1 patient without tumor fully recovered during the follow-up, while residual lesions were left in the other 4 patients with tumors. Conclusions Anti-GABAB receptor encephalitis responds well to immunotherapy, and the early identification, diagnosis and treatment are very important to improve the prognosis of patients. Key words: Gamma-aminobutyric acid; Encephalitis; Epilepsy

Clinical, imaging, and follow-up observations of patients with anti-GABAB receptor encephalitis

Purpose: Anti-gamma-aminobutyric acid B (anti-GABAB) receptor encephalitis is a newly described type of autoimmune encephalitis. We report a case series of patients diagnosed with anti-GABAB receptor encephalitis in China, focusing on their presentations, laboratory and imaging results, and outcomes, as well as the treatment strategies which were employed. Methods: Data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital, School of Medicine, Zhejiang University, from January 2014 to June 2015 were retrospectively collected and analyzed. Based on specific diagnostic criteria, seven cases were included. Results: Six of the seven patients were males, and a median age at presentation of 56 years (range: 4–71 years). Seizures were the most common initial symptom, and all patients developed symptoms of typical limbic encephalitis during their disease course. Additional types of autoantibodies were identified in four patients. After presentation, three patients were found to have small cell lung cancer and one patient was eventually diagnosed with thymoma. All patients accepted first-line immune therapy, but only one chose tumor treatment. The three tumor-free patients had a good outcome, whereas those with tumors had a poor one. Finally, there were no relapses during follow-up. Conclusion: Anti-GABAB receptor encephalitis is a rare, unique autoimmune disease, and is often associated with tumors. It should be considered in the differential diagnosis for middle and senior-aged patients who present with predominantly limbic encephalitis symptoms. Importantly, earlier recognition of this potentially treatable condition could improve its overall prognosis.