The Study Of Cerebrospinal Fluid Neurofilaments Level In Anti-N-methyl-D-aspartate Receptor Encephalitis

ObjectiveNeurofilaments(Nfs)are a series of highly specific scaffolding proteins of neurons,including three subunits named as Nf-heavy chains(Nf-H),Nf-medium chains(Nf-M)and Nf-light chains(Nf-L),respectively.Under the conditions of neurodegeneration or cell death of neuron,Nfs were destroyed and released.Subsequently,Nfs increased in cerebrospinal fluid(CSF)or serum,which were considered as potential effective biomarkers of neuronal damage.Increased Nf-L levels were found in neurological diseases including neuromyelitis optica,multiple sclerosis and Alzheimer’ s disease.However,it is still unclear that whether CSF Nfs in patients with anti-NMDA receptor encephalitis were elevated and whether Nfs were involved in the pathogenesis of this disease.And it remained to be verified that whether Nfs could be used as an objective and effective biomarker to evaluate the severity of disease in the acute phase and the prognosis.Here we aimed to find out that whether CSF Nfs levels in anti-NMDA receptor encephalitis patients,viral meningoencephalitis/encephalitis(VM)patients and in non-inflammatory disease control(NC)group were differrent in the acute phase and whether there was a difference existing in the CSF Nfs levels of anti-NMDA receptor encephalitis patients before and after treatment.Furthermore,the correlation between CSF Nfs level and cytokines or mRS scorce were analyzed to determine whether Nfs could be considered as an objective and effective biomarker to evaluate the severity the disease in the acute phase and prognosis.MethodsWe collected the clinical characteristics,demographic data and anti-NMDA receptor antibody examination in CSF of participants from nanfang hospital,southern medical university.According to the diagnostic standard,exclusion criteria and wheather their CSF were available,we recruited 24 anti-NMDA receptor encephalitis patients(among them 9 were follow-up patients),11 patients with viral meningoencephalitis/encephalitis(VM)and 21 patients in control group(exclude patients with inflammatory diseases).Enzyme-linked immunosorbent assay(ELISA)was conducted to determine the levels of neurofilaments(Nf-L,pNf-H)and cytokines(IL-1,IL-6,IL-17A)in CSF of these three groups of patients,respectively.The same tests and evaluations were repeated in 9 followed-up patients with anti-NMDA receptor encephalitis.We evaluated the clinical outcome or prognosis of the patients according to the modified Rankin scale(mRS)score.SPSS software was used for statistical analysis of the detection results,and Graphpad was used to make statistical graph.ResultsCSF Nf-L(P<0.0001),Nf-H(P=0.004)and cytokines(IL-1,IL-6,IL-17A;their Pvalue were all less than 0.05)levels were significantly higher in patients with anti-NMDA receptor encephalitis than that in control group in acute phase.When compared with VM patients,only Nf-L(P<0.0001)were increased in patients with anti-NMDA receptor encephalitis in acute phase.In addition,the concentration of CSF Nf-L in anti-nmda receptor encephalitis patients in acute phase was positively correlated with the concentration of cytokines(IL-1,IL-17A)and mRS score.Analysis of follow-up patients with anti-NMDA receptor encephalitis showed that the levels of CSF Nf-L,Nf-H,IL-1 β,IL-6,IL-17A in patients with anti-NMDA receptor encephalitis decreased after treatment(P<0.05).During the follow-up period,the levels of Nf-L were still positively correlated with mRS score.Besides,the more CSF Nf-L levels decreased,the more mRS score declined.ConclusionThe level of CSF Nf-L is positively correlated with the clinical outcome and prognosis in patients with anti-NMDA receptor encephalitis which can be used as an objective and effective biomarker to evaluate the severity and prognosis of this disease.Neuronal injury might be involved in the pathogenesis of anti-NMDA receptor encephalitis.The mechanism remains to be further studied.