Study On Regional Homogeneity In School-age And Adolescent Children With Primary Monosymptomatic Nocturnal Enuresis Using Resting-state Functional Magnetic Resonance Imaging

Background and ObjectiveNocturnal enuresis（NE）refers to unconscious leakage of urine during sleep at least once a month in children over 5 years old and lasts for more than 3 months.Primary monosymptomatic nocturnal enuresis（PMNE）is a subtype of nocturnal enuresis,which means that children with NE do not have lower urinary tract symptoms such as daytime frequency,urgency and incontinence,and do not have nocturnal urinary control ability for more than 6 months.In addition to the mismatch between nocturnal urine production and bladder volume,nocturnal sleep-wake disturbance,central cognitive impairment and bladder dysfunction are also important pathogenesis of NE.Previous studies have used Resting state functional magnetic resonance imaging（Rs-fMRI）to analyze the brain function of enuresis children,and found that abnormal changes in brain regions in NE children are related to the above related mechanisms.However,the age span is large,and no in-depth comparative study has been conducted on the brain function of enuresis children of different age subgroups.Regional homogeneity（ReHo）is a parameter in the study of the RsfMRI analysis method,mainly reflects a specific body element and its neighboring voxel synchronization between the changes in brain activity,high stability,with time and space noise sensitive synchronicity,the function of the local area can accurately locate abnormal brain areas,is an important way to resting state of brain function research.In this study,Rs-fMRI technique was used to analyze the brain regions with abnormal brain function in PMNE children by comparing the ReHo differences between PMNE children and normal children.By comparing the differences of ReHo in children with PMNE in different age groups,the differences of brain functional characteristics in school-age and adolescent children with PMNE were analyzed,so as to provide scientific basis for individualized treatment.Methods42 children with PMNE who had never received a formal treatment were recruited for the study.Patients were collected from the Department of Urology,The First Affiliated Hospital of Zhengzhou University from June 2017 to January 2020.According to the age,they were divided into school-age group A（6-11 years old,n=22）,mean age 8.91 ±1.66 years old,10 males,and 12 females,enuresis frequency was 5.8±1.4 times per week;adolescence was in group B（12-17 years old,n=20）,mean age 13.80±1.90 years old,11 males,9 females,enuresis frequency was 5.6 ±1.8 times per week.During the same period,children with upper urinary tract diseases and no urinary tract dysfunction confirmed by urodynamic were included as the control group.They were divided into group C（n=20）of school-age children,with an average age of 8.91 ±1.64 years,10 males and 10 females,and group D（n=20）of adolescent children,with an average age of 14.17±1.99,10 males and 10 females.Rs-fMRI images of all subjects were collected.Firstly,the main effect of the disease,the age and their interaction effects were analyzed using regional homogeneity（ReHo）by Two-way AN OVA.Then,post-hoc tests were performed to compare the differences in brain functional characteristics between groups A and C,groups B and D.Results1.There was no statistical difference in the gender composition of the four groups of data（P>0.05）;There was no significant difference in enuresis frequency between group A and group B（P>0.05）;There was no statistical difference in age between group A and group C,B and D（P>0.05）;Only school-age and adolescent children were statistically different in age（P<0.05）.2.Two-way ANOVA:（1）Disease effect:Left Temporal_Pole_Sup（MNI:x,y,z=-48,18,-9;F=-5.328）,Left Supramarginal gyrus（MNI:x,y,z=-60,-36,39;F=3.865）;（2）Age effect:Right Cingulum_Mid（MNI:x,y,z=6,-21,39;F=-4.911）,Left supplementary motor area（MNI:x,y,z=-3,-6,75;F=3.863）;（3）The brain region of interaction effects were no abnormal.3.Post-hoc analyses:（1）Compared with group C,group A showed increased ReHo values in the Calcarine cortex（MNI:x,y,z=0,-69,21;F=4.675）,decreased in the left vermis₁0（MNI:x,y,z=-3,-42,-36;F=4.860）.（2）Compared with group D,group B showed decreased ReHo values in the Left Temporal_Pole_Sup（MNI:x,y,z=-54,0,0;F=-4.767）,Left Supramarginal gyrus（MNI:x,y,z=-63,-36,33;F=-5.440）,Right Supramarginal gyrus（MNI:x,y,z=60,-30,-30;F=6.451）.Conclusion1.Children with PMNE have abnormalities in brain regions associated with sleep-wake,cognitive function,and bladder dysfunction.2.Cerebellar and occipital lobe functions were abnormal in school-age children with PMNE,and temporal lobe and superior marginal gyrus functions were abnormal in adolescent children.This difference is not related to age factors,suggesting that PMNE children with abnormal function of temporal lobe and superior marginal gyrus are not easy to self-heal,and there are individual differences in enuresis children.Enuresis cannot be simply attributed to a single factor disease.It is necessary but not limited to a detailed assessment of sleep,cognition and bladder function in children,and an individualized treatment plan should be formulated according to the etiology.