Analysis Of Treatment And Prognosis For 20 Patients With Anti-γ-aminobutyric Acid B Receptor Encephalitis

Background:Anti-γ-aminobutyric acid B receptor encephalitis(GABABR)is an autoimmune encephalitis associated with anti-nerve cell surface antibodies,which was first reported by Lancaster in 2010.The incidence of this disease is relatively low,accounting for about 5%of patients with autoimmune encephalitis.The middle-aged and elderly are most frequently affected by anti-GABABR encephalitis.Approximately half of patients with anti-GABABR encephalitis have a history of cancer,and the most common type is small cell lung cancer(SCLC).A small number of patients may also be accompanied by thymoma,melanoma,breast cancer,and esophageal cancer.The limbic system is the most commonly affected area in anti-GABABR encephalitis.Seizures,cognitive impairment and abnormal mental behavior are the main symptoms,and the initial symptom is often seizures.In previous reports,most patients without tumors have a good prognosis after aggressive immunotherapy.First-line immunotherapy includes monotherapy or combination therapy involving corticosteroids,intravenous immunoglobulins(TVIG),or plasma exchange.Some patients who respond poorly to first-line treatment need second-line treatment,such as rituximab(RTX)and cyclophosphamide(CTX).For patients with tumors,in addition to immunotherapy,treatment for tumors has an important impact on the improvement of neurological function and prognosis.Due to the low incidence of anti-GABABR encephalitis,there are few studies on the disease and the understanding for it is relatively limited.Objective:The aim of this study is to to observe the efficacy of immunotherapy and tumor treatment for patients with anti-GABABR encephalitis,to evaluate the correlation between immune cell subsets and disease activity and to investigate effective prognostic factors.Methods:Twenty patients with anti-GABABR encephalitis in the Department of Neurology of Shandong Provincial Hospital Affiliated to Shandong University from December 2015 to April 2020 were enrolled.Collect the clinical data including basic information,clinical symptoms,auxiliary inspection,treatment plans and prognosis.Neurological deficits before and after treatment and during follow-up were evaluated with the modified Rankin Scale(mRS).On the basis of mRS score at the last follow-up,patients were divided into groups with a good prognosis(mRS<2)and poor prognosis(mRS>2),and the clinical parameters between the two groups were compared.Results:(1)In total,twelve patients were male(60%)and eight were female(40%).The average age at disease onset was 59.35±9.20 years(range:35-72 years).In the course of the disease,seizures occurred in 18 cases(90%),14 cases(70%)developed mental and behavioral abnormalities,17 cases(85%)were accompanied with cognitive impairment,awareness impairment was observed in 14 case(70%).Furthermore,ataxia and brainstem encephalitis was documented in 1 case(5%)and 1 case(5%),respectively.Brain magnetic resonance imaging(MRI)demonstrated abnormalities on T2-weighted imaging(T2WI)and fluid-attenuated inversion recovery(FLAIR)located in temporal lobe,hippocampus,and medulla oblongata in 11 cases(55%),In addition,15 cases(75%)had abnormal electroencephalography(EEG).(2)Twenty patients(100%)received first-line immunotherapy.The median mRS scores were 4(3-5)and 3(2-5)before and after first-line immunotherapy(P<0.01).In the cohort,there were twelve patients(60%)with tumors,all of which were SCLC.Nine patients received tumour treatment,and five of them died.The median time from the diagnosis of encephalitis to death of the five patients was 15(10-36)months.After a median follow-up period of 11.5(range:3-20)months,the neurological function of the four surviving patients who received tumour treatment showed good outcomes(mRS≤2).All three patients who did not receive tumour treatment died,and the median time from the diagnosis of encephalitis to death was 5(3-7)months.Among the patients who died because of tumours,patients who received tumour treatment lived longer than those who did not receive tumour treatment(P=0.025).(3)The median CD19+B-cell counts in peripheral blood prior first-line immunotherapy were 20.00%in sixteen patients and in remission were 13.42%in fourteen patients(P<0.01).(4)After a maximum follow-up of 54 months(range:3-54),eleven patients(55%)had a poor prognosis(mRS>2).Predictors of a poor prognosis were older age(P=0.031),delayed initial improvement after immunotherapy(P=0.038)and respiratory failure(P=0.038).Conclusion:Aggressive immunotherapy and tumour treatment contribute to improvements in neurological function and a better prognosis of patients with anti-GABABR encephalitis.The CD19+B-cell counts may be an indicator of disease activity.Older age,delayed initial improvement after immunotherapy(>4 weeks),and respiratory failure may be associated with poor outcomes.