Alterations Of Brian Function,AQP4-IgG Subtype Distribution And Prevention Treatment Of Neuromyelitis Optica Spectrum Disorders

Objective:1)The aim of this study was to use resting-state functional magnetic resonance imaging(fMRI)to investigate changes of spontaneous brain activity in myelin oligodendrocyte glycoprotein antibody(MOG-Ab)related disorder,and differentiate it from neuromyelitis optica spectrum disorders(NMOSDs).2)Using monoclonal peptides to neutralize the cytotoxicity of APQ4-IgG,investgate the different subtypes distribution in serum of NMOSDs patients,aiming to discovery a novel way to prevent the binding of AQP4 and AQP4-IgG to treat NMOSDs.3)This study aims to evaluate the efficacy and safety of repeated treatments with low-dose rituximab for relapsing neuromyelitis optica spectrum disorder(NMOSDs)and look for a better therapy strategy,compared with MMF and AZA.Result:1)Compared with HCs,all patients with MOG-Ab related disorder or NMOSDs had significantly increased ALFF values in the prefrontal gyrus.Patients with MOG-Ab related disorder showed additional hyperactive in motor cortex and somatosensory cortex,comparing to NMOSDs and HCs.2)Serum of 33 patients were collected.Using monoclonal peptides to neutralize the cytotoxicity of APQ4-IgG,there were 6 subgroup according to different subtypes distributions.There were 11 patients with all anti-Loop IgG,8 patients with anti-LoopA IgG and anti-LoopC IgG,2 patients with anti-LoopA IgG and anti-LoopE Ig,8 patients with anti-LoopC IgG and anti-LoopE IgG,2 patients with anti-LoopC IgG and 2 patients with anti-LoopE-IgG.There were no difference within subgroups on onset age,worst onset BCVA,recovery BCVA,nor auto-immune antibody ratio.Divided patients into other three subgroups according to anti-Loop counts.Mono-antibody had better recovery BCVA than other two groups,there were no difference on the other clinical features.3)109 patients were enrolled and were followed-up more than two years.Compared with previous EDSS,FSS and ARR before the treatment,EDSS and FSS remained same,ARR were reduced in all groups.Strictly following the treatment stredgies,the order of effectiveness within these three groups was MMF=RTX>AZA,the order of safety within these three groups was MMF>RTX>AZA.Conclusion:1)Hyperactivity in prefrontal cortex,motor cortex and somatosensory cortex might reflect differences in pathological processes between MOG-Ab related disorders and NMOSDs.fMRI could provide new evidence of possibly multi-focal disease mechanisms.2)Most of patients had more than one subtype.There is no significant difference between each groups.Using monoclonal peptides can neutralize the cytotoxicity of APQ4-IgG in cell culture.3)The treatment of NMOSDs with lose-dose RTX,MMF and AZA could reduce the frequency of relapses and are well tolerated.The therapy should be individually designed and performed accordingly.