Analysis Of Clinical Manifestations And Prognosis Of MOG-IgG Associated Disorders With Fever

Objective: Fever is a deceptive feature of autoimmune diseases.MOG-IgG associated disorders(MOGAD)in pediatric cases are often accompanied with fever.Fever can even be the main manifestation in the early stage in some cases.These cases were often misdiagnosed,leading to delay in immunity treatment.We investigated the clinical characters and prognosis of MOGAD with fever and explored the relationship between infection and MOGAD,to provide clinical experience for early identification and timely diagnosis and treatment.Methods:Children patients diagnosed as MOGAD were enrolled in the study in Children’s Hospital of Chongqing Medical University from2014 to 2019,divided into fever group and non-febrile group.Analyzed and compared the differences and prognosis between the two groups.The recovery of neurologic function was evaluated by EDSS.The data analysis was carried out by SPSS 23.0 software,and the statistical significance was found with P < 0.05.Results:71 children diagnosed as MOGAD were included.(1)General Information:The male to female ratio was 1:1.22.The age of onset was 1.6-15.3 years,and the average age was 8.75±2.98 years.18% of children had a history of pre-infection or vaccination before the onset of illness,which was not statistically different between the fever group and the non-febrile group.(2)Clinical features:The top three onset symptoms of MOGAD were fever(34%),vision impairment(18%)and headache(18%).The mainly clinical symptoms were fever(63%),encephalopathy(61%)and headache(61%).Fever was the most common clinical manifestation of MOGAD.63% of children accompanied with fever.69%of them had fever for more than 1 week.49% of children lasted for more than 2 weeks,and 6 cases(8%)behaved as fever of unknown origin.(3)45cases were enrolled in the fever group.The most 3 common symptoms were dizziness and headache(78%),encephalopathy(67%)and motor dysfunction(51%).The most frequent phenotype at onset were ADEM(60%)、encephalitis(other than ADEM)(20%)and ON(16%).3 cases were diagnosised as cortical encephalitis(7%).26 cases were enrolled in the non-febrile group.The most 3 common symptoms were vision impairment(50%),motor dysfunction(50%)and encephalopathy(50%).The most frequent phenotype were ADEM(54%)、ON(35%)and encephalitis(other than ADEM)(12%).No cortical encephalitis case was seen.(4)Compared with the non-febrile group:(1)Clinical manifestations: Dizziness and headache(P<0.001)and disturbance of consciousness content(P=0.042)in the fever group were more obvious.Cortical encephalitis was more often.(2)Blood routine: The increased WBC count(P=0.014)and CRP(P=0.044)were more common,and manifested as the dissociated inflammatory markers(elevated white blood cells and low CRP levels);(3)Cerebrospinal fluid: Elevated WBC count was more common in children in the fever group(P=0.013),and it could be manifested mainly as increased multinucleated cells(P=0.015);(4)Head MRI: Lesions in basal ganglia(P=0.032)and corpus callosum(P=0.042)were more obvious in fever group.In children with fever lasted for more than 1 week,thalamus lesions(P=0.029)were more common.8% of children in fever group have normal or atypical appearance on MRI at the onset,and typical demyelinating lesions appeared after 5-30 days.(5)Prognosis: Relapse rate in fever group(40%)was higher than that in non-febrile group(23%).The main relapse symptom in fever group was seizures(33%),and in non-febrile group were motor dysfunction(67%)、ataxia(50%)and vision impairment(33%).But there were no statistical difference between the two groups.(5)Infection and MOGAD: 23% children found pathogen in blood or cerebrospinal fluid(Ig M positive or PCR elevated).5 cases of children had intracranial infection,including 2 cases of EBV,2 cases of CVB,1 case of VZV,1 case of JEV.3 cases found MOG antibody positive and pathogen at the same time.2 cases with EBV encephalitis detected MOG antibody positive 10-22 days after the pathogen was detected;11 cases had pathogen positive in blood and negative in cerebrospinal fluid,including 7 cases of EBV,4 cases of CVB,1 case of HSV,and 1 case of CMV.The interval between pathogen and MOG antibody detection was6-20 days,and 5 cases were detected at the same time.55% of children had EBV-IgG positive in cerebrospinal fluid,and 71% had EBV-IgG positive in blood.The positive rate of EBV-IgG antibody in the cerebrospinal fluid of children in fever group was higher(P=0.008).No case had bipolar course.Conclusion:(1)MOGAD in pediatric cases often starts with fever,and even has a long-term continuous fever as the main symptom.Some children may only present with fever of unknown origin.Fever in MOGAD often lasted more than 1 week.(2)Compared with the non-febrile cases:MOGAD with fever has more obvious symptoms of dizziness,headache,and disturbance of consciousness content.The blood routine often manifests as the dissociated inflammatory markers(elevated white blood cells and low CRP.Cerebrospinal fluid may have meningitis-like manifestations.Head MRI in MOGAD with fever can atypical and be misdiagnosed as infectious diseases.It is necessary to be highly vigilant for such children,and complete the head MRI and MOG antibody detection as soon as possible.(3)Relapse rate in fever group is slightly higher than that in non-febrile group.Children in fever group are more likely appear seizures when relapse.(4)Viral infection can induce MOGAD,and Epstein-Barr virus is the most common pathogen.The mechanism is unclear.MOGAD secondary to Epstein-Barr virus encephalitis can be manifested as long-term fever,lacking the typical bipolar course and neurological dysfunction.