anti-GABABR Encephalitis Research Articles

Novel findings of HLA association with anti-LGI1 encephalitis: HLA-DRB1*03:01 and HLA-DQB1*02:01

This study was to investigate whether autoimmune encephalitis is associated with the human leukocyte antigen (HLA) genotypes in Chinese Han population. We compared and analyzed the HLA genotypes of 101 patients with autoimmune encephalitis (77 anti-NMDAR, 11 anti-LGI1 and 13 anti-GABABR antibody, respectively) to the 200 healthy control groups. Our results showed that the DRB1*03:01 or DQB1*02:01 allele and the extended DRB1*03:01 ~ DQB1*02:01 haplotype represented the strong susceptibility locus for anti-LGI1 encephalitis (OR = 18.84, 95% CI = 5.01–70.89, Pc = 0.004; OR = 18.84, 95% CI = 5.01–70.89, Pc = 0.004; OR = 18.84, 95% CI = 5.01–70.89, Pc = 0.001). Additionally, the DRB1*08:03 ~ DQB1*06:01 or B*08:01 ~ C*07:02 haplotype was likely to be associated with anti-LGI1 encephalitis (OR = 10.23, 95% CI = 2.87–36.42, Pc = 0.039; OR = 74.62, 95% CI = 6.97–799.06, Pc = 0.043). No statistically significant differences were found for HLA association between patients with anti-NMDAR or anti-GABABR encephalitis and healthy controls. These results indicated that HLA subtypes were only associated with anti-LGI1 encephalitis.

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 of the seizures in the neuronal surface antibody-associated autoimmune encephalitis - Report of 18 Cases

To investigate clinical features of seizures in different types of neuronal surface antibody-related autoimmune encephalitis (AE). The clinical data of seizures in 18 cases of neuronal surface antibody-related AEs diagnosed in our hospital were retrospectively analyzed. Among 18 cases, 9 was LGI1 antibody-related encephalitis, 1 anti-GABABR encephalitis, 6 anti-NMDAR encephalitis, and 2 AE with undefinable antibodies. Epileptic seizures in 9 cases of LGI1 antibody-associated AE manifested in 3 forms: faciobranchial dystonia seizure (FBDS) in 4, mesial temporal lobe epilepsy (MTLE) in 6, and GTCS in 7 patients. The brain MRI of 4 patients showed high T2 flair signal on one hippocampus, 2 showed high T1/T2 signal on one side basal ganglia. For EEG, 6 revealed interictal epileptic discharges; ictal EEG were recorded in 5 patients, 2 FBDS, 3 MTLE. Epileptic seizures in patient with anti-GABABR encephalitis manifested in 2 forms: GTCS and MTLE. Epileptic seizures in 6 cases of anti-NMDAR encephalitis manifested in 2 forms: partial seizures in 3, GTCS in 5 cases. For EEG, 2 cases showed interictal epileptic discharges, 3 showed δ activity or rhythm in frontal area. Most neuronal surface antibody-associated AE have seizures. LGI1 antibody-associated AE usually affected limbic system or basal ganglia, seizure type accordingly were MTLE or FBDS. Anti-GABABR encephalitis showed severe and refractory seizures, GTCS or MTLE, which rapidly progress to status epilepticus and AEDs were ineffective. Anti-NMDAR encephalitis showed more generalized than partial seizures. The δ activity or rhythm in frontal area in EEG was helpful for diagnosis.

Encephalitis With Antibodies Against the GABAB Receptor: High Mortality and Risk Factors.

Objective: To measure mortality, identify predictors of death and investigate causes of death in patients with anti-gamma-aminobutyric-acid B receptor (anti-GABABR) encephalitis.Methods: Prospective analysis of anti-GABABR encephalitis cases diagnosed between June 2013 and August 2018 in West China Hospital of Sichuan University, with assessment of factors associated with mortality.Results: A total of 28 patients (11 females) with anti-GABABR encephalitis were included in this study. After a maximum time of 52 months (median 11 months, range 2–52) of follow-up, 9 (32.1%) patients died, with a median survival time of 6.5 months. Five patients died of tumor progression, one patient died of convulsive status epilepticus, one patient died of septic shock, and two patients died of severe pneumonia. Predictors of death were older age at onset (P = 0.025), presence of a tumor (66.7 vs. 15.8%, P = 0.013), the number of complications (2.6 vs. 1.0, P = 0.009) and deep venous thrombosis (33.3% vs. 0, P = 0.026).Conclusion: Patients with GABABR encephalitis have a high mortality rate within 5 years. Older age at onset, presence a tumor, the number of complications, and deep venous thrombosis are associated with death.

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.

The expanded clinical spectrum of anti-GABABR encephalitis and added value of KCTD16 autoantibodies.

In this study we report the clinical features of 32 patients with gamma aminobutyric acid B receptor (GABABR) antibodies, identify additional autoantibodies in patients with anti-GABABR encephalitis that mark the presence of an underlying small cell lung carcinoma and optimize laboratory methods for the detection of GABABR antibodies. Patients (n = 3225) were tested for the presence of GABABR antibodies using cell-based assay, immunohistochemistry and live hippocampal neurons. Clinical data were obtained retrospectively. Potassium channel tetramerization domain-containing (KCTD)16 antibodies were identified by immunoprecipitation, mass spectrometry analysis and cell-based assays. KCTD16 antibodies were identified in 23/32 patients with anti-GABABR encephalitis, and in 1/26 patients with small cell lung carcinoma and Hu antibodies, but not in 329 healthy subjects and disease controls. Of the anti-GABABR encephalitis patients that were screened sufficiently, 18/19 (95%) patients with KCTD16 antibodies had a tumour versus 3/9 (33%) anti-GABABR encephalitis patients without KCTD16 antibodies (P = 0.001). In most cases this was a small cell lung carcinoma. Patients had cognitive or behavioural changes (97%) and prominent seizures (90%). Thirteen patients developed a refractory status epilepticus with intensive care unit admittance (42%). Strikingly, 4/32 patients had a rapidly progressive dementia. The addition of KCTD16 to the GABABR cell-based assay improved sensitivity of the in-house fixed cell-based assay, without loss of specificity. Twenty-two of 26 patients improved (partially) to immunotherapy or chemotherapy. Anti-GABABR encephalitis is a limbic encephalitis with prominent, severe seizures, but patients can also present with rapidly progressive dementia. The co-occurrence of KCTD16 antibodies points towards a paraneoplastic origin. The addition of KCTD16 improves the sensitivity of the cell-based assay.

Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis.

ObjectiveThis nationwide cohort study evaluates seizure responses to immunotherapy and antiepileptic drugs (AEDs) in patients with anti-leucine-rich glioma-inactivated 1 (LGI1), anti-NMDA receptor (NMDAR), and anti-gamma-aminobutyric-acid B receptor (GABABR) encephalitis.MethodsAnti-LGI1, anti-NMDAR, and anti-GABABR encephalitis patients with new-onset seizures were included. Medical information about disease course, AEDs and immunotherapies used, effects, and side effects were collected. Outcome measures were (1) seizure freedom while using AEDs or immunotherapy, (2) days to seizure freedom from start of AEDs or immunotherapy, and (3) side effects.ResultsOf 153 patients with autoimmune encephalitis (AIE) (53 LGI1, 75 NMDAR, 25 GABABR), 72% (n = 110) had epileptic seizures, and 89% reached seizure freedom. At least 53% achieved seizure freedom shortly after immunotherapy, and 14% achieved seizure freedom while using only AEDs (p < 0.0001). This effect was similar in all types (p = 0.0001; p = 0.0005; p = 0.013, respectively). Median time to seizure freedom from AEDs start was 59 days (interquartile range [IQR] 27–160), and 28 days from start of immunotherapy (IQR 9–71, p < 0.0001). Side effects were psychotic behavior and suicidal thoughts by the use of levetiracetam, and rash by the use of carbamazepine. Carbamazepine was more effective than levetiracetam in reducing seizures in anti-LGI1 encephalitis (p = 0.031). Only 1 patient, of 86 surviving patients, developed epilepsy after resolved encephalitis.ConclusionEpilepsy after resolved encephalitis was rare in our cohort of patients with AIE treated with immunotherapy. In addition, seizure freedom is achieved faster and more frequently after immunotherapy. Therefore, AEDs should be considered as add-on treatment, and similar to treatment of other encephalitis symptoms, immunotherapy is crucial.

Characteristics of Seizure and Antiepileptic Drug Utilization in Outpatients With Autoimmune Encephalitis.

Autoimmune encephalitis (AE) is one kind of encephalitis that associates with specific neuronal antigens. Most patients with AE likely suffer from seizures, but data on the characteristics of seizure and antiepileptic drugs (AEDs) utilization in this patient group remains limited. This study aimed to report the clinical status of seizure and AEDs treatment of patients with AE, and to evaluate the relationship between AEDs discontinuation and seizure outcomes. Patients with acute neurological disorders and anti-N-methyl-D-aspartate receptor (NMDAR), γ-aminobutyric acid B receptor (GABABR), leucine-rich glioma inactivated 1, or contactin-associated protein-like 2 (CASPR2) antibodies were included. As patients withdrew from AEDs, they were divided into the early withdrawal (EW, AEDs used ≤3 months) and late withdrawal (LW, AEDs used >3 months) groups. Seizure remission was defined as having no seizures for at least 1 year after the last time when AEDs were administered. Seizure outcomes were assessed on the basis of remission rate. The factors affecting the outcomes were assessed through Spearman analysis. In total, we enrolled 75 patients (39 patients aged <16 years, male/female = 39/36) for follow-up, which included 67 patients with anti-NMDAR encephalitis, 4 patients with anti-GABABR encephalitis, 2 patients with anti-voltage-gated potassium channel encephalitis, and 2 patients with coexisting antibodies. Among the 34 enrolled patients with anti-NMDAR encephalitis who were withdrawn from AEDs, only 5.8% relapse was reported during the 1-year follow-up, with no significant difference in the percentage of relapse between the EW and LW groups (P = 0.313). Fifteen patients (an average age of 6.8, 14 patients with anti-NMDAR encephalitis and 1 patient with anti-CASPR2 encephalitis) presented seizure remission without any AEDs. Seventy five percent of patients with anti-GABABR antibodies developed refractory seizure. Other risk factors which contributed to refractory seizure and seizure relapse included status epilepticus (P = 0.004) and cortical abnormalities (P = 0.028). Given this retrospective data, patients with AE have a high rate of seizure remission, and the long-term use of AEDs may not be necessary to control the seizure. Moreover, seizures in young patients with anti-NMDAR encephalitis presents self-limited. Patients with anti-GABABR antibody, status epilepticus, and cortical abnormalities are more likely to develop refractory seizure or seizure relapse.

Encephalitis with antibodies against the GABAB receptor: seizures as the most common presentation at admission

Objective: Autoimmune encephalitis associated with antibodies against gamma-aminobutyric-acid B receptor (GABABR) has not been described in detail in Chinese patients. Methods: Patients with anti-GABABR encephalitis treated between January 2013 and December 2015 were analyzed in terms of clinical characteristics, laboratory findings, tumor presence, autoantibody patterns, treatment response and outcomes. Results: Eleven patients were identified (male, N = 8; female, N = 3), with the median age of 51 years. All patients presented with seizures (N = 11; 100%), and they were given anti-epileptic drugs and first-line immunotherapy to address the disease. Seizures always accompanied by limbic manifestations (N = 10; 90.9%). Extralimbic manifestations were present in 4 patients (N = 4; 36.4%). MRI Brain abnormality with increased medio-temporal lobe T2/FLAIR signal were present in 2 patients (N = 2; 18.2%), and epileptiform epileptiform activity on electroencephalography were observed in 2 patients (N = 2; 18.2%). Small-cell lung cancer was histologically confirmed in 3 patients (N = 3; 27.3%). Seven patients showed good outcomes (mRS 1–2; N = 7; 63.6%), one patient showed poor neurological status with minimal changes (mRS 4; N = 1; 9.1%), and three patients died during follow-up (mRS = 6; N = 3; 27.3%). Outcomes were correlated with age-of-onset, and were worse among older patients (P = 0.0112). Conclusion: Anti-GABABR encephalitis is a potentially treatable disorder involving seizures as the most predominant presentation at admission. It should be considered as a possible diagnosis in middle-aged and older patients with refractory new-onset epilepsy.