The Efficiency Of Rituximab In The Treatment Of Anti-NMDA Receptor Encephalitis Without Tumour

Background:Since the first description of autoimmune encephalitis with N-methyl-D-aspartate receptor autoantibodies(NMDAR)encephalitis in young women with ovarian teratomas,the spectrum of this disease has been concerned by many experts.This autoimmune disorder was thought to affect young female predominately who accompany with ovarian teratomas.With increased recognition,the phenotype has broadened to men,children and older individuals with acute/subacute neurological or psychiatric deficits.Moreover,the occurrence of tumour depend on age and sex.Although anti-NMDAR encephalitis has a risk of death,almost 80%of patients can receive a substantial neurological improvement after the resection of tumour or immuotherapy.Two independent predictors of good outcome were no need for admission to an intensive care unit,and the prompt initiation of immunotherapy and tumour removal.Titulaer and colleagues demonstrate that about 50%of patients had no improvement with first-line treatments.Thus,experts suggest:for these patient second-line immunotherapy include rituxiamab,mycophenolate mofetil or azathioprine is needed.Rituximab is a monoclonal antibody directed against the CD20 surface antigen expressed on pre-B lymphocytes.Its mechanism includes cell-mediated and complement dependent cytotoxic effects and the induction of apoptosis to prevent the maturation of pre-B cells into antibody-secreting cells.In recent years,it has been widely used in CNS autoimmune and inflammatory disease,clear evidence has demonstrated it can improve clinical progress and decrease relapse.Objective:The aim of this study was to evaluate the efficacy and safety of rituximab for treating anti N-methyl-D-aspartate receptor(NMDAR)encephalitis without tumours.Methods:10 patients with anti-NMDAR encephalitis without tumour were hospitalized between May 1,2014 and April 30,2015 at the Department of Neurology,Shandong Provincial Hospital affiliated to Shandong University and they showed no respond to 10 days first-line immunotherapy(corticosteroids and intravenous immunoglobulins,IVIG)and received rituximab therapy.Clinical features and investigations of these patients were retrospectively reviewed.The therapeutic regimen of rituximab was 100 mg IV infusion,once per week for 4 consecutive week.Modified rankin scale(mRS),the percentage of CD19+ B cells among the total lymphocytes and immunoglobulins level were monitored after the last infusion of rituximab.Then the interval for monitoring mRS,the percentage of CD19+ B cells and immunoglobulins level was extended to 8-10 weeks.Reinfusion of rituximab was given when CD19+ B-cell counts of total lymphocyte in peripheral blood>1%.By assessing pre-and postrituximab annualized relapse rate(ARR),mRS score,CD19+ B-cell counts,immunoglobulins level and infusion adverse event to evaluate the efficiency and safety of rituximab.Results:(1)During the course of the disease,8 cases(80%)presented with abnormal psychiatric/behavior or cognitive dysfunction,5 cases(50%)experienced seizure,5 cases(50%)showed decreased level of consciousness,3 cases(30%)presented with speech dysfunction,4 cases(40%)experienced autonomic dysfunction or central hypoventilation,7 cases(70%)showed movement disorder.Initial MR1 were abnormal in 4(40%)patients with fluid-attenuated inversion recovery(FLAIR)or T2 weighted imaging(T2WI)hyperintensity signals located in the hippocampi,occipital lobes,temporal lobe.CSF was abnormal in 7(70%)cases.The EEG was abnormal in 5(50%)cases.(2)At the last follow up,mRS score and CD19+ B-cell counts of total lymphocyte in peripheral blood were a median of 1(range 0-1.25)and 0.93(range 0.74-1.91)%respectively as compared with 4.5(4-5)and 15.60(range 11.71-21.14)%before rituximab treatment(P<0.05).The ARR pre-and post-rituximab were a median of 0(0-1)and 0(0-0)(P>0.05).6 patients received repeated rituximab treatment.Lower dosages of rituximab kept 9(90%)patients a stabilized neurological status.Only patient 3 experienced relapsed at 19 weeks after initial rituximab infusion.At the last follow up,9 cases(90%)had a good outcome(mRS<2)and 3 cases(30%)recovered completely(mRS=0).Transient infusion adverse events occurred in two patients.We observed no serious delayed adverse events during the 56 weeks follow-up.Conclusions:In patients with anti-NMDAR encephalitis who did not respond to first-line immunotherapy,early application of rituximab could efficiently reduce CD19+B-cell counts of total lymphocyte and improve the prognosis of anti-NMDAR encephalitis.