Correlation Between NLR,MLR And Severity Of Disease In Patients With Autoimmune Encephalitis

Background and purposes:Autoimmune encephalitis(AE)is an autoimmune inflammatory disease targeting neuronal cell surface or synaptic proteins in the central nervous system.The clinical manifestations of AE are complex and diverse,mainly including seizures,mental and behavioral disorders,consciousness disorders,speech disorders,autonomic nervous dysfunction,cognitive dysfunction and involuntary movements.Furthermore,AE is a disease that has significant clinical heterogeneity,and this disease progresses rapidly in some patients,which may be life-threatening due to central hypoventilation or severe autonomic dysfunction within weeks or even days.However,studies on biological indicators of the severity of AE is still in its infancy,and an objective and inexpensive biomarker is urgently needed to guide clinical practice.The neutrophil-to-lymphocyte ratio(NLR)is a biomarker derived from blood routine to reflect the inflammatory status of the body.Several studies have shown that NLR is closely related to the severity and prognosis of patients with AE.Nevertheless,in these studies,patients were assessed using the Modified rankin scale(mRS),which takes motor function as the main indicator.In addition to motor dysfunction,patients with AE may also present with a variety of non-motor symptoms such as mental and behavioral disorders,seizures,consciousness disorders and speech disorders.Therefore,there are great limitations in the assessment of AE with the mRS.The Clinical Assessment Scale for Autoimmune Encephalitis(CASE)is a new assessment scale designed for AE in 2019,which compensates for the deficiencies of the mRS in assessing non-motor symptoms of AE.Moreover,the criteria of the CASE are more detailed and specific,which can assess the severity of disease in different stages more accurately.The monocyte-to-lymphocyte ratio(MLR)is a new inflammatory marker similar to NLR discovered in recent years.A Korean study on endometrial cancer displayed that high levels of MLR were prominently associated with cancer recurrence and cancer-related death.Interestingly,it has also been found to be associated with the severity and activity of some immune-related diseases such as multiple sclerosis,systemic lupus erythematosus,axial spondyloarthritis and ulcerative colitis.However,it is unclear whether MLR correlates with the severity of AE.This study aimed to summarize the clinical characteristics of AE and analyze the association of NLR and MLR with the severity of AE.Study subjects and methods:This study included patients diagnosed with AE in the First Affiliated Hospital of Zhengzhou University from October 2015 to October 2021.The clinical data on age,gender,clinical manifestations(including seizures,mental and behavioral disorders,consciousness disorders and speech disorders)and auxiliary examinations were collected.Routine blood tests were performed in all patients within 24 hours after admission.NLR=neutrophils/lymphocytes,MLR=monocytes/lymphocytes.Grouped patients with AE according to the CASE.Mild group:CASE≤4 points;severe group:CASE≥ 5 points.Receiver operating characteristic curve(ROC)was used to evaluate the power of NLR and MLR in predicting the severity of AE,and Area under the curve(AUC)was calculated.The clinical characteristics of AE were summarized as well as the correlation of NLR and MLR with the severity of AE was analyzed.Results:A total of 199 patients with AE were enrolled in this study,including anti-NMDAR encephalitis(59.8%),anti-LGI1 encephalitis(20.6%),and anti-GABABR encephalitis(19.6%).1.The median onset ages of anti-NMDAR,anti-LGI1,and anti-GABABR encephalitis were(28,61,and 61.5)years,respectively,and the age of onset of anti-NMDAR encephalitis was prominently lower than that of anti-LGI1 and anti-GABABR encephalitis.The proportion of males was 55.5%,73.2%,and 66.7%,respectively,and there was no statistical difference in gender ratio among the three groups.The ratio of seizures in anti-NMDAR,anti-LGI1,and anti-GABABR encephalitis was 42.0%,58.5%,and 71.8%,respectively,and the percentage of seizures in anti-GABABR encephalitis was significantly higher than that of anti-NMDAR encephalitis.The proportion of mental and behavioral disorders was 72.3%,46.3%,and 84.6%,respectively,and the ratio of mental and behavioral disorders in anti-NMDAR and anti-GABABR encephalitis was significantly higher than that of anti-LGI1 encephalitis.The proportion of consciousness disorders was 36.4%,22.0%,and 61.5%,respectively,and the percentage of consciousness disorders in anti-GABABR encephalitis was significantly higher than that of anti-NMDAR and anti-LGI1 encephalitis.The percentage of speech disorders was 62.2%,24.4%,and 51.3%,respectively,and the ratio of speech disorders in anti-NMDAR and anti-GABABR encephalitis was significantly higher than that of anti-LGI1 encephalitis.The CASE(median)scores were(6,3,and 5)points,respectively.The mRS(median)scores were(3,2,and 3)points,respectively.The mRS scores in anti-NMDAR and anti-GABABR encephalitis were significantly higher than that of anti-LGI1 encephalitis.The ratio of severe patients was 56.3%,31.7%,and 56.4%,respectively,and the proportion of severe patients in anti-NMDAR encephalitis was significantly higher than that of anti-LGI1 encephalitis.2.The white blood cells,neutrophils,monocytes,NLR,and MLR of the severe group were significantly higher than those of the mild group,and lymphocytes were lower than that of the mild group.The NLR and MLR of anti-NMDAR,anti-LGI1 and anti-GABABR encephalitis in severe group were significantly higher than those of mild group.3.Spearman correlation analysis showed that NLR and MLR were positively correlated with the CASE scores in AE patients(r=0.659,P<0.001;r=0.533,P<0.001),and subgroup analysis showed that NLR and MLR were positively correlated with the CASE scores in anti-NMDAR encephalitis(r=0.694,P<0.001;r=0.535,P<0.001),anti-LGI1 encephalitis(r=0.590,P<0.001;r=0.571,P<0.001),and anti-GABABR encephalitis(r=0.482,P=0.002;r=0.629,P<0.001).The NLR and MLR were positively correlated with the mRS scores in AE patients(r=0.609,P<0.001;r=0.478,P<0.001),and subgroup analysis showed that NLR and MLR were positively correlated with the mRS scores in anti-NMDAR encephalitis(r=0.648,P<0.001;r=0.468,P<0.001),anti-LGI1 encephalitis(r=0.542,P<0.001;r=0.632,P<0.001),and anti-GABABR encephalitis(r=0.525,P=0.006;r=0.529,P=0.001).The CASE was validated,and the results showed that the CASE scores were positively correlated with the mRS scores in AE,anti-NMDAR,anti-LGI1 and anti-GABABR encephalitis.The correlation coefficient was(r=0.849,P<0.001;r=0.868,P<0.001;r=0.741,P<0.001;r=0.778,P<0.001),respectively.The CASE scores had a wider distribution than the mRS scores and was also widely distributed among patients with the same mRS score.4.The AUC of NLR for assessing severe AE,anti-NMDAR,anti-LGI1,and anti-GABABR encephalitis were 0.827,0.859,0.835,and 0.756,respectively;the AUC of MLR for assessing severe AE,anti-NMDAR,anti-LGI1,and anti-GABABR encephalitis were 0.771,0.763,0.808,and 0.849,respectively;and the AUC of NLR combined with MLR were 0.840,0.866,0.849,and 0.849,respectively.5.NLR(OR=1.475,95%CI:1.211-1.796,P<0.001)and MLR(OR=15.228,95%CI:1.654-140.232,P=0.016)were independent risk factors for patients with severe AE.Conclusions:1.The NLR of patients with severe AE is significantly higher than that of mild patients,and the elevation degree can reflect the severity of the disease.High NLR is an independent risk factor for severe AE.2.The MLR of patients with severe AE is significantly higher than that of mild patients,and the elevation degree can reflect the severity of the disease.High MLR is an independent risk factor for severe AE.3.Both the CASE and the mRS can be used to evaluate the severity of AE,while the CASE has greater sensitivity over than the mRS.