Review Of Ancient Literature On Brain-spirit-qi And Clinical Validation Of Multimodal MRI In Multiple System Atrophy And Parkinson's Diseas

Objective:(1)Through combing the ancient literature of brain marrow,brain spirit and brain Qi,this paper provides literature and theoretical basis for the understanding and development of brain marrow-spirit-Qi theory.Understand multiple system atrophy(MSA)and parkinson’s disease(PD)from the perspective of brain marrow-spirit-Qi and put forward common core pathogenesis and treatment.(2)To explore the relationship between the imaging characteristics of multimodal MRI of MSA and PD and the brain marrow-spirit-Qi injury.(3)To study the effect of warming kindney and strengthening brain Recipe on the clinical efficacy and mechanism of action of MSA and PD,and to verify the core pathogenesis of brain marrow-spirit-Qi injury.Research methods:(1)Combing ancient literatures related to brain marrow,brain spirit and brain qi,collecting and summarizing literatures related to brain marrow,brain spirit and brain qi in ancient books;According to the time axis from Qin and Han Dynasties to Ming and Qing Dynasties,this paper combs the ancient documents vertically,and combs the different ancient medical books in each period horizontally.Sort out its development context in ancient times,analyze and summarize the development characteristics of different periods.Combined with the research of ancient literature and the views of modern doctors,this paper looks for the relationship between the clinical symptoms of MSA and PD patients and brain marrow,brain spirit and brain Qi,establishes the common core pathogenesis of the two diseases,and expounds the medication basis of warming kindney and strengthening brain recipe.(2)Structural and resting fMRI techniques were used to observe the differences between patients with MSA and PD and HC,and combined with the correlation between brain regions of interest and scales(UMSARS,UPDRS,MOCA scale)to find the relationship with brain marrow-Spirit-Qi injury.Voxel based morphometry(VBM)analysis method was used to observe the changes of brain microstructure and find the relationship with brain spinal cord injury;Based on the analysis of ALFF value and ReHo value,the changes of spontaneous activity of brain neurons in patients were observed to find the relationship with brain injury;Analyze the whole brain large-scale network connection,observe the strength of brain functional connection,and find the connection with brain Qi injury.(3)The patients with MSA and PD who met the screening criteria were treated with warming kindney and strengthening brain formula for 3 months.The scores of TCM syndrome score,MoCA scale,PSQI scale,FSS scale and geriatric depression(GDS)scale,unified multiple system atrophy Rating Scale(UMSARS)of MS A group and Multiple system atrophic non motor symptom scale(msa-NMSS),Unified Parkinson Disease Rating Scale(UPDRS)and the non motor symptoms scale(NMSS)in PD group were used to evaluate the clinical efficacy of warming kindney and strengthening brain recipe.The patients with MSA and PD were randomly selected for structural and fMRI examination before and after treatment to evaluate the mechanism of warming kindney and strengthening brain formula and verify the core pathogenesis of brain marrow-Spirit-Qi injury.Results:Part Ⅰ:The theory of brain marrow,brain spirit and brain Qi was initially summarized and formed in the era of Neijing,which was inherited by later generations,including the discussion and play of the relationship between brain marrow and kidney essence,brain Qi and Qi and blood.With the emergence of metaphysics and the prevalence of Taoism and Buddhism,the understanding of brain Spirit and brain Qi in Wei,Jin,Sui and Tang Dynasties tended to be metaphysical and theological.During the song,Jin and Yuan Dynasties,influenced by the academic atmosphere and printing technology,some medical works were greatly promoted,and the theories of brain marrow,brain spirit and brain Qi were further enriched.Li Shizhen’s proposal of "the brain is the house of the yuan Spirit" is an important node in the development history of this theory.In the Ming and Qing Dynasties,the discussion books on the theory of brain marrow,brain spirit and brain Qi developed towards specialization and systematization,and there were also in-depth explanations on its functions and the relationship between viscera.The development of this theory entered a new and relatively complete stable period.Part Ⅱ:There were 78 patients with MSA、17 patients with PD and 27 healthy controls.(1)From the perspective of brain microstructure,compared with HC,it can be seen that the main brain areas with reduced cortical volume are in the orbital part of the middle frontal gyrus,the middle temporal gyrus,the fusiform gyrus and the anterior cingulate gyrus in MSA group,and in the thalamus,cerebellum,the middle temporal gyrus,the orbital surface of the inferior frontal gyrus,the anterior cingulate gyrus and the fusiform gyrus in PD group.In addition,in MSA and PD groups,the cortical volume decreased in the middle temporal gyrus,infrafrontal gyrus,orbital surface and anterior cingulate gyrus.Because the frontotemporal lobe is associated with memory function,the anterior cingulate gyrus is associated with somatic motor area.Therefore,in terms of morphological volume reduction and symptoms,cognitive decline and gait disorder caused by kidney deficiency,marrow damage and naoxiao are the manifestations of brain marrow-Spirit-Qi injury in traditional Chinese medicine,mainly brain marrow injury.(2)From the spontaneous activity of brain neurons,compared with HC,in the brain areas with abnormal activity,MSA group showed that the ALFF value of right fusiform gyrus,left middle temporal gyrus,bilateral inferior temporal gyrus and bilateral hippocampus decreased,the ReHo value of left middle frontal gyrus decreased,and the ReHo value of right anterior cingulate gyrus,right medial superior frontal gyrus,left anterior cingulate gyrus and left medial superior frontal gyrus increased.In PD group,the ALFF values of bilateral fusiform gyrus,bilateral inferior temporal gyrus,right middle temporal pole,right parahippocampal gyrus and left middle temporal gyrus decreased,the ReHo values of right insula decreased,and the ReHo values of right middle occipital lobe,right middle temporal gyrus and right inferior temporal gyrus increased.In addition,both MSA and PD groups had abnormal neuronal activities in visual and speech functional areas,which was the manifestation of brain marrow-Spirit-Qi injury in traditional Chinese medicine,mainly brain Spirit injury.(3)From the perspective of brain network connection,compared with the healthy group,the network connection functions of ventral attention network and marginal network were lower in MSA group(P<0.05),and the network connection functions of sensory/somatic motor network and ventral attention network were lower in PD group(P<0.05).From the function of sensory and somatic motor networks,the loss of connection between networks,the sensory abnormalities of clinical symptoms(frequent urination,second fecal incontinence,etc.)and the symptoms of physical fatigue are the manifestations of brain marrow-Spirit-Qi injury in traditional Chinese medicine,mainly brain Qi injury.(4)Based on the putamen,globus pallidus and cerebellum as regions of interest,the volume of bilateral putamen and right globus pallidus in MSA group was negatively correlated with the score of UMSARS scale,and the volume of cerebellar area 7(right)was positively correlated with the score of MoCA scale.In PD group,the volume of cerebellar area 7(right)was negatively correlated with the score of UPDRS,and the volume of bilateral putamen,right globus pallidus and cerebellar area 7(right)was positively correlated with the score of MoCA.Part Ⅲ:116 patients were finally included in this study,including 73 patients with MSA and 43 patients with PD.24 patients with MSA and 11 patients with PD were selected for structural and functional magnetic resonance imaging before and after treatment.(1)General data:there were more men than women in patients with MSA.The average age of onset was 53.36±8.12 years,and the course of disease was 4 years;The average age of onset was 62.21±7.84 years,and the course of disease was 5 years.(2)Main outcome measures efficacy analysis:a total of 116 patients were included.After 3 months of treatment,the total scores of main and secondary symptoms of TCM syndrome scores decreased(P<0.05).The main symptoms are silent,joyless and speechless,fatigue,fatigue,tremor or unstable holding,frequent urination,excessive nocturnal urination or urinary incontinence;dizziness,insomnia,tepid limbs,weak stool or dry knot were significantly improved(P<0.05).The score of MSA decreased significantly in the primary and secondary analysis groups.The scores of primary and secondary symptoms in PD group decreased compared with those before treatment(P<0.05).The total score of MoCA scale increased,and the scores of attention,language function,abstraction and delay function in sub items increased compared with the previous ones(P<0.05).The score of PD group was lower than that of MSA group(P>0.05).The total score of PSQI decreased(P<0.05),and the scores of sleep quality,sleep time,hypnotic drugs,sleep disorders and daytime dysfunction decreased(P<0.05).Group analysis showed that the scores of MSA group and PD group decreased compared with the previous group(P<0.05).The total score of FSS scale decreased(P<0.05).Grouping analysis showed that the score of FSS scale decreased in MSA group and PD group after treatment(P<0.05).The total score of GDS scale decreased(P<0.05).Grouping analysis showed that the score of GDS scale decreased in MSA group and PD group after treatment(P<0.05).Efficacy analysis of secondary outcome measures:the total scores of UMSARS-Ⅰ and UMSARS-Ⅱ in MSA group were higher than before.The symptoms progressed faster in language,writing,cutting food,dressing,hygiene and walking,and body shaking,but the growth rate was slower compared with previous studies.The scores of NMSS scale decreased after treatment(P<0.05),and the scores of defecation,sweating,sleep and psychosomatic aspects decreased(P<0.05).The UPDRS-Ⅱ score and UPDRS-Ⅲscore of PD group decreased compared with those before treatment,and the tremor score decreased compared with those before treatment,with no statistical difference.In UPDRS-Ⅲscore,rigidity,hand movement,rotation,flexible legs and abnormal posture decreased compared with those before treatment(P<0.05).The PD-NMSS score decreased after treatment(P<0.05).(3)The changes of brain miucrostructure in MSA group and PD group before and after traditional Chinese medicine treatment were compared by VBM analysis,and there was no significant difference,indicating that the structural "brain Qi" injury is irreversible.In terms of the changes of spontaneous activity of brain neurons,the ALFF values of left talus gyrus,lingual gyrus,right central sulcus cover,insula,superior temporal gyrus and anterior temporal gyrus increased in MSA group;The ReHo values of left central posterior gyrus and left central anterior gyrus increased(P<0.001);In PD group,the ALFF values of lateral lenticular globus pallidus,left thalamus and left lenticular putamen increased,and the ReHo values of right orbital inferior frontal gyrus,right inferior frontal gyrus triangle,right caudate gyrus,right insula and right middle frontal gyrus increased.This enhancement of neuronal activity proves the role of "brain Spirit" in traditional Chinese medicine.In terms of the changes of functional connections of large-scale brain networks,the average intra network connections of sensory somatic motor networks and visual networks in MSA group were significantly enhanced after treatment,which proved the role of "brain Qi" in traditional Chinese medicine.Conclusion:(1)In the Qin and Han Dynasties,the theory of brain marrow-spirit-Qi was initially formed,involving the discussion of source,function,syndrome differentiation and treatment,etc;From then on to the Song Dynasties,Jin and Yuan Dynasties,the theory of brain marrow spirit Qi was further enriched;During the Ming and Qing Dynasties,the brain marrow-spirit-Qi theory was perfected.The formula of warming kindney and strengthening brain based on brain marrow-spirit-Qi injury has a certain theoretical basis for the treatment of MSA and PD.(2)MSA and PD have abnormal brain microstructure,spontaneous activity of local brain neurons and brain network connection,which is a manifestation of brain marrow-spirit-Qi injury in traditional Chinese medicine.(3)The prescription for warming the kidney and strengthening the brain based on the brain marrow-spirit-Qi injury can delay the disease progression of MSA and PD patients,effectively improve the symptoms of cognition,sleep and fatigue,and have a good regulatory effect on the spontaneous activity of brain neurons and the functional connection of brain networks in MSA and PD patients.