Clinical Characteristics And Prognosis Of Mog-IgG-related Disorders And AQP4-IgG-positive NMOSD

Background and objectiveOptic myelitis spectrum disorders(NMOSD)is a kind of central nervous system(CNS)demyelinating disease mediated by auto-immune inflammatory,most commonly affects the optic nerve and spinal cord,but also affects the area postrema.Its core clinical manifestations include unilateral or bilateral optic neuritis,myelitis,area postrema syndrome,acute brainstem syndrome,etc.The prevalence of female is significantly higher than that of male.As detection sensitivity and specific degree of AQP4 IgG and MOG IgG rise,some studies have found positive serum MOG-IgG in some NMOSD patients with negative serum AQP4-IgG,and at the same time,some MOG-IgG-positive patients show clinical characteristics different from NMOSD.With the further development of research,experts at home and abroad now agree that MOGAD is an independent disease entity,rather than a variant of MS or NMOSD.Although the clinical manifestations of MOGAD patients and NMOSD patients may partially overlap,their pathogenesis,demographic characteristics,typical symptoms and prognosis are different.MOGAD can be uniphasic or recurrent,presenting with optic neuritis,myelitis,meningoencephalitis,brainstem encephalitis and other symptoms,and its prognosis is often different from that of NMOSD patients.At present,there are still few domestic studies on the comparison of the clinical characteristics of NMOSD and MOGAD.This study aims to explore the demographic,symptomatology,MRI and laboratory characteristics of MOG-IgG-related diseases and AQP4-IgGpositive NMOSD,as well as the factors associated with their prognosis.MethodsDemography,clinical data,imaging examinations,serum and cerebrospinal fluid tests of MOGAD and serum AQP4-IgG positive NMOSD patients admitted to the Fifth Affiliated Hospital and the First Affiliated Hospital of Zhengzhou University from January 2017 to March 2020 were retrospectively collected,and followed up for a period of 6-36 months.Serum AQP4-IgG or MOG-IgG were detected by cell-based indirect immunofluorescence assay(CBA)for all enrolled patients.3.0T brain and spinal cord MRI examinations were performed,and the images were read and recorded by two experienced radiologists.(1)To investigate the differences between AQP4-IgGpositive NMOSD patients and MOGAD patients in demographic characteristics,first symptoms,clinical manifestations,imaging features,cerebrospinal fluid and serological tests;(2)Spearman rank correlation was used to analyze the correlation between EDSS score of the end of follow-up and clinical features,imaging features,serum and cerebrospinal fluid indexes in MOGAD group and AQP4-IgG positive NMOSD group.IBM SPSS26.0 statistical software was used for all statistical analyses,and a P < 0.05 was considered statistically significant.Results1.The median age of first onset in the MOGAD group was 26 years old,including24 female patients(58.54%).The ratio of female to male was 1.4:1.The median age of first onset in the AQP4-IgG positive NMOSD group was 37.5 years,including 174females(85.29%),and the female-male ratio was 5.8:1.There were significant differences between the two groups in the first age,the proportion of children and adolescents,the proportion of men and women,and the proportion of patients with preinfection history(P<0.05).2.The most common first-onset symptoms of MOGAD group are ON(34.15%)and meningoencephalitis-like symptoms(34.15%),followed by myelitis(21.95%),brainstem syndrome(7.32%),and lethargia(2.44%);The most common first-onset symptom in the AQP4-IgG-positive NMOSD group is myelitis(42.16%),followed by ON(32.84%).The area postrema syndrome is the first attack symptom in 14.71% of the patients,the brainstem syndrome in 7.84% of the patients,and the meningoencephalitis-like symptoms in 2.45% of the patients.The proportion of patients with encephalitis/meningoencephalitis-like manifestations as the first-onset symptoms in MOGAD group is significantly higher,in which the proportion with fever with headache and epilepsy as the first-onset symptoms is significantly higher,and the proportion with myelitis and area postrema syndrome as the first symptoms is significantly lower than that in AQP4-IgG positive NMOSD group,the difference is statistically significant(P<0.05).3.The proportion of myelitis in MOGAD group is significantly lower than that in AQP4-IgG-positive NMOSD group,and the proportion of patients with weakness,numbness or hypoesthesia,dysuria,trunk or limb pain is significantly lower than that in AQP4-IgG-positive NMOSD group,while the proportion of patients with epilepsy is significantly higher than that in AQP4-IgG-positive NMOSD group(P<0.05).There is no significant difference in the proportion of ON,brainstem syndrome,area postrema syndrome,cerebral symptoms and diencephalic symptoms between the two groups.4.In patients with abnormal head MRI,the involvement of thalamus,corpus callosum,cerebral hemisphere and cerebellum in MOGAD group is significantly higher than that in AQP4-IgG positive NMOSD group,and the involvement of paraventricular third,paraventricular fourth and midbrain water channel is significantly lower than that in AQP4-IgG positive NMOSD group,with statistical significance(P<0.05).There is no significant difference in the proportion of brain MRI abnormalities between the two groups.The proportion of spinal cord lesions in MOGAD group(60.98%)is significantly lower than that in AQP4-IgG positive NMOSD group,and the proportion of spinal cord lesions involving lumbar cord is significantly higher than that in AQP4-IgG positive NMOSD group,with statistical significance(P<0.05).There is no significant difference in the proportion of cervical cord lesions and thoracic cord lesions between the two groups.5.The proportion of patients with increased lumbar puncture pressure in MOGAD group(26.83%)is significantly higher than that in AQP4-IgG positive NMOSD group(7.35%),and the increase of CSF white blood cell count in 63.41% MOGAD group is significantly higher than that in AQP4-IgG positive NMOSD group,with statistical significance(P<0.05).There is no significant difference between the two groups in other cerebrospinal fluid tests.6.Serological test: MOGAD group,21.95% of patients with combined other autoantibody positive,major is given priority to with thyroid related antibodies and antinuclear antibody positive,AQP4-66.18% IgG positive NMOSD groups have merged other autoantibodies in patients with positive,antinuclear antibodies,anti SSA,RO52 antibody resistance,anti SSB antibody is given priority to,combined other autoantibody positive patient proportion between two groups have significant difference(P < 0.05),while the proportion of patients with abnormal thyroid structure or function and serum virus antibody positive patients ratio has no significant difference.7.Prognosis: Compared with the AQP4-IgG-positive NMOSD group,the total number of attacks in the MOGAD group was less,the proportion of patients with recurrence course was relatively lower(53.66%),the total number of recurrence was less,the annualized recurrence rate of patients in the recurrence group was higher,and the EDSS score was lower at the time of interception,the difference was statistically significant(P < 0.05).Spearman correlation analysis shows that the EDSS score of the MOGAD group is positively correlated with myelitis as the first symptom,the interval between the first recurrence and the first attack,and the involvement of the spinal cord MRI lesion.The correlation coefficients r are 0.536,0.425,0.339,respectively,With statistical significance(P<0.05).The factors in the AQP4-IgG positive NMOSD group and the intercepted EDSS score and their correlation coefficients are: IgG production index(0.543),24-hour IgG synthesis rate(0.474),age of first episode(0.400),spinal cord The number of lesions involving the longest continuous vertebral body segment(0.342),lesions involving the thoracic cord(0.291),time between first recurrence and first attack(0.272),myelitis as the first symptom(0.248),IgG quotient(0.216),CSF Percentage of monocytes(0.199),CSF OCB(0.198),CSF IgG(0.187),lesion involving the lumbar spinal cord(0.165);the factors that have a significant negative correlation with the intercepted EDSS score and their correlation coefficient r are: CSF White blood cell count(-0.285),serum albumin(-0.269),percentage of CSF lymphocytes(-0.251),brain MRI lesions(-0.229),last zone syndrome as the first symptom(-0.206),CSF albumin(-0.204),blood virus antibody positive(-0.177),meningoencephalitis-like symptoms as the first symptom(-0.162),statistically significant(P<0.05).Conclusion1.MOGAD and AQP4-IgG-positive NMOSD have different demographic characteristics,clinical manifestations,imaging characteristics,cerebrospinal fluid and blood test results and different prognosis.Compared with AQP4-IgG-positive NMOSD patients,MOGAD patients first developed at a younger age,with a higher proportion of juvenile patients.With more ON the symptom or encephalitis/ meningoencephalitis,less to myelitis or final area,the onset of the syndrome lesions involving the spinal cord ratio is low,is often involving waist marrow,intracranial lesions less involvement NMOSD typical parts such as the third ventricle,near the fourth ventricle,midbrain aqueduct,etc.,and involved the thalamus,corpus callosum,cerebral hemisphere and cerebellum is more,less merged other autoantibody positive,lumbar puncture pressure increased and cerebrospinal fluid leukocyte increased more,often better prognosis.2.The poor prognosis of patients with MOGAD and AQP4-IgG-positive NMOSD is positively correlated with the longer interval between first attack and recurrence and with myelitis as the first attack symptom.