Analysis Of Clinical Characteristics And Clinical Functional Outcome Associated Factors Of Patients With Autoimmune Encephalitis

Autoimmune encephalitis（AE）refers to a group of encephalitis mediated by autoimmune mechanisms^[1].The concept of"limbic lobe encephalitis"was first introduced by Corsellis in 1968^[2],and the recognition of AE was enhanced by Buckly’s report of patients with undetectable tumors in limbic encephalitis in 2001^[3].Since 2007,anti-NMDAR antibody encephalitis and various AE have been reported.AE accounts for 10%～20%of encephalitis cases.Not only the prevalence of AE is increasing year by year,but also the clinical symptoms are severe,so it is important to further analyze the characteristics of the disease and factors related to clinical functional outcomes for early diagnosis and treatment.Objective:（1）To statistically analyze the clinical characteristics of patients with AE in our hospital since March 2017,（2）To statistically analyze the factors associated with clinical functional outcomes in patients with AE.Methods:Patients with AE who met the diagnostic criteria for AE proposed by Graus et al.in Lancet Neurol in 2016 and the AE diagnostic criteria in the 2017 Chinese Expert Consensus on the diagnosis and treatment of autoimmune encephalitis were collected from March 2017to October 2022 in the Department of Neurology of our hospital.The general data,clinical manifestations,and ancillary examinations of the patients were collected for statistical analysis,the clinical characteristics of AE were counted,telephone follow-up was performed,and the patients were evaluated based on the modified Rankin Scale score（m RS）.m RS score 0-2 was classified as the good functional outcome group,and 3-6 was classified as the poor functional outcome group.The risk factors were first analyzed by univariate correlation analysis using SPSS 26.0 software,and the statistically significant factors in the univariate analysis were brought into logistic regression analysis to determine the factors associated with clinical functional outcome.Results:（1）Among the total 157 AE patients with positive antibodies,52%（82 cases）were male and 48%（75 cases）were female,with no significant gender differences.Anti-NMDAR antibody encephalitis accounted for 24%（37 cases）with a mean age of 40.11±16.90 years old,anti-LGI1 antibody encephalitis accounted for 32%（50 cases）with a mean age of61.10±11.93 years old,anti-GABA_BR antibody encephalitis accounted for 22%（34 cases）with a mean age of 58.32±12.79 years old,anti-CASPR2 antibody encephalitis accounted for5%（8 cases）with a mean age of 42.63±16.84 years old,anti-GAD65 antibody encephalitis accounted for 6%（10 cases）with a mean age of 49.80±19.65 years old,rare and combined antibody encephalitis accounted for 11%（18 cases）with a mean age of 54.00±17.27 years old.Rare and non-combined antibody patients included anti-AMPAR2（2 cases）,anti-m Glu R5（2 cases）,anti-Ri（1 case）,anti-Hu（1 case）and anti-CV2 antibodies（1 case）.Patients with double and multiple antibody positivity included anti-GABA_BR combined with anti-SOX1（3 cases）,anti-NMDAR combined with anti-MOG（2 cases）,anti-NMDAR combined with anti-GABA_BR（2 cases）,anti-NMDAR combined with anti-CASPR2（1 case）,anti-GAD combined with anti-Hu（1 case）,anti-m Glu R5 combined with anti-DPPX（1 case）and anti-SOX1 combined with anti-CV2 and anti-GQ1b antibodies（1 case）.The results showed that anti-NMDAR antibody encephalitis was mostly seen in young and middle-aged patients,anti-LGI1,anti-GABA_BR,rare and combined antibody encephalitis were all prone to occur in middle-aged and elderly patients aged 51 to 70 years old,and anti-CASPR2antibody and anti-GAD antibody-related encephalitis were mostly seen in middle-aged patients.（2）Among the 157 patients,some patients had prodromal symptoms（29%）,mainly including headache（6%）,dizziness（5%）,respiratory symptoms（4%）,fever（6%）,digestive symptoms such as diarrhea,nausea,vomiting and anorexia（4%）,and rare prodromal symptoms such as drowsiness,blurred vision,precordial discomfort,neck discomfort,olfactory and visual hallucination,fatigue and so on.The initial symptom was epilepsy in 54%of patients,the seizures could be generalized seizures,aphasic seizures,focal seizures,FBDS,muscle twitching in the face and other areas,foreign body sensation in the mouth with involuntary movements,shaking of the limbs and so on.Followed by abnormal mental behavior（13%）,cognitive impairment（14%）,which could be manifested as memory loss,decreased calculation power,slow reaction and disorientation,headache（2%）and other forms of onset（17%）including ocular symptoms,numbness,sensory abnormalities,fever,impaired consciousness,sleep disturbances,dizziness,nausea and vomiting,clumsy speech,and respiratory difficulties.Seizures（72%）,abnormal psychiatric behavior（50%）,cognitive decline（46%）,and impaired consciousness（37%）were the main clinical features throughout the course of the disease,in addition,there were fever（20%）,headache（14%）,diffuse or multifocal brain damage manifestations,speech abnormalities,sleep abnormalities,and ocular symptoms.（3）Among the 157 patients,95%（149 cases）performed head MRI and 51%（76 cases）had normal head MRI.Of the 49%（73 cases）patients with visible lesions on head MRI,35%（52 cases）involved the hippocampus,temporal lobe,or insula.and the remaining 14%（21cases）had lesions in the frontal,parietal,basal ganglia region,parietal ventricle,cerebellum,cerebellum,corpus callosum,corona radiata,thalamus,midbrain,centrum semiovale,occipital lobe,white matter,and sulcus.A total of 92%（145 cases）patients have taken EEG examination,and 94%（137 cases）had abnormal EEG results,mainly including decreased brain function and focal discharges,of which spike waves,spike slow waves and slow waves were common.The head MRI and EEG results were not statistically significant between the good functional outcome group and the poor functional outcome group.（4）A total of 18%（28 cases）of the included patients had tumors,among which anti-NMDAR antibody encephalitis and anti-LGI1 antibody encephalitis were mainly combined with tumors of the reproductive system,which could be teratoma,uterine leiomyoma and prostate cancer,anti-GABA_BR,anti-GAD65 and rare and combined antibody encephalitis patients were mainly combined with small cell lung cancer.Other systemic tumors include thymoma,esophageal cancer and renal pelvis cancer.（5）The length of hospitalization was 17（12,23）days,11%（17 cases）developed respiratory failure during the course of the disease,and 40%（63 cases）were treated in the intensive care unit.22%（35 cases）of 157 patients were treated with glucocorticoids alone,15%（24 cases）were treated with intravenous immunoglobulin（IVIg）alone,36%（56 cases）were treated with combined first-line immunotherapy（combination of 2 or more regimens of glucocorticoids,IVIg and plasma exchange）,14%（22 cases）were treated with first-line immunotherapy combined with anti-tumor therapy,1 patient applied first-line immunotherapy and second-line immunotherapy（intravenous cyclophosphamide）,1 patient applied only anti-tumor therapy and did not agree to immunotherapy,and another 11%（18patients）received only symptomatic supportive treatment without immunotherapy and anti-tumor therapy.（6）Among the 157 patients,20 patients experienced recurrence,17 patients of whom experienced one recurrence and 3 patients of whom experienced two recurrences during the course of their disease.A total of 32 patients died during the follow-up until now,including 1patient who died during hospitalization,12 patients who died due to recurrent seizures after discharge,7 patients who died due to cancer,and 13 patients who died due to their own underlying diseases or unknown causes.1 patient developed femoral head necrosis due to glucocorticoid shock and is currently treated with traditional Chinese medicine.（7）Univariate correlation analysis of various ancillary tests revealed that age,antibody type,presence or absence of tumor,CSF antibody titer,CSF protein,Qa Ib actual value,hs-CRP,NLR,EO,cholesterol,LDL-C,ALB,and whether or not admitted to the intensive care unit had statistical difference between the good functional outcome group and the poor functional outcome group.The good functional outcome group had younger patients,higher prevalence of anti-LGI1 antibody encephalitis,lower rate of tumor consolidation,lower CSF antibody titers,lower CSF protein levels,lower Qa Ib actual values,lower hs-CRP levels,smaller NLR values,higher EO,lower cholesterol levels,lower LDL-C levels,higher ALB levels,and lower intensive care unit admissions.（8）Multi-factor logistic regression equations were constructed by incorporating statistically significant indicators of univariate correlation analysis age,antibody type,presence of concomitant tumor,and cerebrospinal fluid antibody titer,and the results showed a good effect of model fit superiority.The five variables of age,EO,hs-CRP,cholesterol,and whether to admit to the intensive care unit were found to have a statistically significant effect on clinical functional outcome.The higher the age,the higher the risk of poor functional outcome,which was statistically different（OR=1.090,95%CI 1.026-1.158,P=0.005）,the lower the absolute level of EO,the higher the risk of poor functional outcome（OR=0.898,95%CI 0.813-0.992,P=0.034）,the higher the hs-CRP level,the higher the risk of poor functional outcome（OR=1.052,95%CI 1.011-1.095,P=0.012）,the higher the cholesterol index,the higher the risk of poor functional outcome,with statistical difference（OR=7.101,95%CI 1.091-46.229,P=0.040）,relative to those who had not admitted to the intensive care unit,patients who had been treated in the intensive care unit during the course of the disease had a statistically higher risk of poor functional outcome（OR=7.157,95%1.288-39.762,P=0.024）.Conclusion:（1）Anti-NMDAR antibody encephalitis is mostly seen in young and middle-aged patients,while other types of AE are mostly seen in middle-aged and elderly patients.The prodromal symptoms include mainly headache,dizziness,respiratory and digestive symptoms.The disease usually starts with epilepsy,abnormal mental behavior and cognitive decline.Seizures,abnormal mental behavior,cognitive decline and impaired consciousness are the main clinical manifestations during the course of the disease.（2）Head MRI mostly shows abnormal signals in hippocampus,temporal lobe and insula.EEG mostly indicates decreased brain function and focal discharges.Anti-NMDAR antibody encephalitis and anti-LGI1 antibody encephalitis are mainly combined with genital tumors,anti-GABABR,anti-GAD65 and rare and combined antibody encephalitis patients are mainly combined with lung cancer,other systemic tumors include thymoma,esophageal cancer,renal pelvic kidney cancer and so on.（3）The five variables of age,EO,hs-CRP,cholesterol,and admission to the intensive care unit for treatment were associated with clinical functional outcome in patients with AE.