To Explore The Mechanism Of Bushen Yisui Method On Multiple System Atrophy From The Perspective Of Brain Marrow-brain-qi-brain-shen

Objective:(1)To observe the difference of resting state functional magnetic resonance imaging(rs-fMRI)between patients with multiple system atrophy(MSA)and Healthy control(HC),as well as the difference between MSA-cerebellar type and MSA-parkinsonian type,in order to provide a basis for the early diagnosis of MSA.Correlation analysis was conducted with clinical scales to explore the correlation between patients' symptoms and functional disconnection of certain brain regions.Besides,the connection between Brain marrow-Brain qi-Brain spirit theory and MSA patients was also explored.(2)From the perspective of Brain marrow-Brain qi-Brain spirit theory,combined with relevant scales and fMRI examination to observe the clinical efficacy and mechanism of the treatment of MSA by tonifying kidney and nourshing marrow.(3)Under the tasking state fMRI to observe the effect of acupuncture at Taixi Point(KI3)on the brain functional activities of MSA patients,to explore the mechanism and specificity of acupuncture at KI3 based on the method of tonifying kidney and nourshing marrow,so as to provide an objective basis for the exposition of Brain marrow-Brain qi-Brain spirit theory.Method:(1)Through fMRI technology to explored the differences in spontaneous activity of brain neurons between MSA patients and HC.Functional connectivity(FC)of the whole brain was carried out based on the region of interest,and seed points were selected to measure FC among MSA patients at various brain regions,so as to explore the differences in activity of different brain regions.The large-scale network connections were analyzed in order to explore FC of whole brain.Pearson correlation test was used to analyze the correlation between FC in different brain regions with Unified Multiple System Atrophy Rating Scale(UMSARS)and Montreal Cognitive Assessment(MOCA),in order to explore the correlation between clinical symptoms,cognitive level and brain dysfunction.Besides,the differences of neuron spontaneous activity in patients with different subtypes of MSA were compared.(2)MSA patients according with inclusion and exclusion criteria were selected to participate in this study.UMSARS-I,UMSARS-II,UMSARS-II total score(?+?),Multiple System Atrophy-Non-Motor Symptom Scale(MSA-NMSS),Over Active Bladder Symptom Scale(OABSS),and supine-vertical blood pressure were assessed before treatment,1 month and 3 months after treatment to evaluate the effect of tonifying kidney and nourshing marrow on motor symptoms,non-motor symptoms,supine and vertical blood pressure and urination symptoms of MSA patients.Meanwhile,according to grouping criteria to subdivide patients into subgroup for discussion.Besides,some patients were randomly selected for fMRI examination before and after treatment to evaluate the mechanism of the method of tonifying the kidney and nourshing marrow.In addition to,compared with MSA patients in the previous study of pure Chinese herbal treatment to observe the differences in brain functional activities between these two methods(3)Subjects meeting the inclusion and exclusion criteria were selected for acupuncture at Taixi point(KI3)under fMRI technology,and needle sensation was assessed after the process.Compared with acupuncture at KI3 on HC and sham acupuncture at MSA to observe the effect of acupuncture at KI3 on the brain damaged area of MSA patients.Results:(1)From the aspect of neurons spontaneous activity,imaging showed that bilateral cerebellum posterior lobe,left cuneus were decreased at regional homogeneity(REHO)value,bilateral calcarine,lingual gyrus,anterior cingulum gyrus,inferior frontal orbital gyrus,left precuneus,left cuneus,right precentral were decreased at amplitude of low frequency fluctuation(ALFF)value,and negative correlation suggested between these brain regions with UMSARS.However,the cerebrum can compensate through a large number of projection connections to cerebellum,so ALFF value may increase in the left anterior lobe and bilateral posterior lobe.From the aspect of partly FC,compared with HC,the cerebral FC of MSA patients decreased in the right inferior temporal gyrus,middle temporal gyrus,bilateral posterior cerebellar lobe,inferior frontal orbital gyrus,inferior frontal triangle gyrus,middle frontal gyrus,posterior cingulate gyrus,left precuneus and supplementary motor area.And bilateral superior parietal lobule,postcentral were increased.The functional connection between the middle frontal gyrus and precuneus was positively correlated with the MOCA score.In terms of the whole brain network FC,the default mode network(DMN),sensorimotor network and subcortical network FC were enhanced,as well as the subcortical network and visual network.But the frontal parietal control network and DMN FC were impaired.In terms of subtype analysis,the ALFF values of MSA-P type in left middle occipital gyrus,parietal inferior gyrus,angular gyrus and occipital superior gyrus were higher than those of MSA-C type.The REHO value of bilateral posterior lobe of cerebellum,left inferior temporal gyrus,middle temporal gyrus,angular gyrus and middle occipital gyrus were increased.(2)After 1 month of treatment,the total scores of UMSARS-?,UMSARS-? and UMSARS-?+? in 3 subgroups were increased to different degrees compared with before treatment,but the difference was not statistically significant(P>0.05).Even though,the increase was still less than the natural course of MSA.And the higher the severity of the disease,the faster the progress can grow.In terms of the scores of each item,fall and tension were decreased with statistical significance(P<0.05).The total score of MSA-NMSS in the three subgroups decreased after treatment with statistical significance(P<0.05),and the symptoms of fatigue,frequent urination,difficult defecation,dry stool,RBD,insomnia and other symptoms were improved to varying degrees with statistical significance(P<0.05).The total OABSS score slightly increased compared with before treatment,but the difference was not statistically significant(P>0.05).In terms of the scores of each item,the frequency of urgent urination decreased compared with before,and was statistically significant(P<0.05).In terms of blood pressure,the patients' systolic blood pressure in supine position was increased compared with before,but the difference was not statistically significant(P>0.05),and the systolic blood pressure in vertical position was also increased compared with before,and the difference was statistically significant(P<0.05).Diastolic blood pressure in supine position also increased compared with before,and the difference was statistically significant(P<0.05).At the same time,systolic and diastolic blood pressure differences in supine and vertical positions were decreased compared with before,but the differences were not statistically significant(P>0.05).After 3 months of treatment,the total scores of UMSARS-?,UMSARS-? and UMSARS-?+? in 3 subgroups were higher than before,and the increase was statistical difference in subgroup 2(P<0.05).In terms of the scores of each item,the scores of fall was decreased with statistically significant(P<0.01),while the scores in urinary system function,increased tension,leg flexibility and body shaking decreased slightly compared with before,but the difference was not statistically significant(P>0.05).Although the score was little improved,the increase was still less than the natural progression of MSA.The total score of MSA-NMSS in the three subgroups decreased after treatment with statistical significance(P<0.05),and muscle soreness,salivation,dizziness/syncopation in the standing(or sitting)position,frequency of urination,insufficiency of urination,difficult defecation,dry stool,RBD,insomnia and memory loss decreased with statistical significance(P<0.05).The patients whose MSA-NMSS score was lower than that before treatment accounted for 82.61%of the total number.The total OABSS score was increased compared with before.Urinary urgency was decreased but the difference was not statistically significant(P>0.05).Urinary incontinence was increased and the change was statistically significant(P<0.05),which indicated that bladder abnormalities caused by neurogenic damage were not easy to relieve.The systolic blood pressure and diastolic blood pressure of patients in the supine position were increased compared with before,but the difference was not statistically significant(P>0.05).The difference of systolic blood pressure in supine and vertical position was lower and the difference was statistically significant(P<0.05).Diastolic pressure difference in supine position was also decreased,but the difference was not statistically significant(P>0.05).In addition,according to fMRI,after treatment with kidney-tonifying therapy,there was an increase in ReHo value in the precuneus and superior parietal gyrus of MSA patients.Compared with the treatment of pure Chinese herbal therapy,the activation of neurons in occipital lobe was more significant.(3)Needle sensation assessment showed that the feeling was more strongly when twisting needle,and HC had felt more than the number of patients,especially at the feeling like electric shock,VAS score was also significantly higher than that of patients,and aching feeling was more frequent than the number of HC.Besides,the two groups both felt soreness,numbness,distention,electric shock and stabbing pain,and the VAS score were moderate.After acupuncture with KI3,ALFF value at bilateral thalamus and caudate nucleus were increased in MSA patients,while REHO value at bilateral lingual gyrus,calcarine,posterior lobe of cerebellum,left middle occipital gyrus,inferior occipital gyrus,middle temporal gyrus,superior temporal gyrus and right fusiform gyrus were decreased.However,no brain regions were found with REHO value increased.After sham acupuncture,the ReHo value only decreased at right lingual gyrus,which proved the existence of acupoint specificity.In addition,acupuncture KI3 can increase the Reho value in the anterior cerebellar lobe,striatum,thalamus and hippocampus of HC,and the decreased area of ReHo value was basically consistent with verum acupuncture of MSA.Conclusion:(1)There truly had abnormalities in the spontaneous activity of neurons in specific brain regions and the abnormalities in the connection of the whole brain network in MSA,which may be the basic neural mechanism of MSA occurring movement disorders,cognitive decline and emotional abnormalities,and is expected to become a potential biomarker for the clinical diagnosis of MSA.Besides,this study also confirmed the existence of Brain marrow-Brain qi-Brain spirit theory in MSA patients.(2)Kidney tonifying and marrow nourshing therapy could delay the progression of the disease,and the earlier the treatment began,the slower the progression growth.At the same time,it can also effectively improve patients' non-motor symptoms,significantly improve patients' orthostatic systolic blood pressure,decrease differential pressure,which caused by postural changed,so as to reduce the incidence of syncope and falls.However,after the intervention of tonifying kidney and nourishing marrow,the connection between the visual area and the body movement in MSA patients was strengthened,which improved the patients'falling,body shaking and memory loss.Compared with pure Chinese herbal treatment,the visual compensation was enhanced thus fall was better improved.(3)Brain regions related to movement and memory in HC were activated immediately after acupuncture,while the ReHo value of MSA in same regions was not changed,which indicated the severity of brain neuron loss in patient.The damage of white matter fiber connection and the atrophy of brain regions related to sports and cognition are positively correlated with the brain marrow injury to a certain extent.Moreover,it takes a long time for the brain marrow to be replenished,so the immediate effect cannot be achieved after acupuncture.However,the spontaneous activity of patients' neurons in a large number of brain regions was changed after acupuncture,which confirmed the existence of brain spirit.The regulation effect of acupuncture KI3 on the visual region may also be related to the promotion of brain Qi.Therefore,this study once again confirmed the existence of Brain marrow-Brain qi-Brain spirit theory in MSA patients,and acupuncture may improve the clinical symptoms by affecting Brain marrow-Brain qi-Brain spirit in patients,but the specific mechanism still needed further study.