The Case Series Study And Preliminary Study On The Brain Mechanism Of Improving Tourette Syndrome By Acupuncture With "Soothing Liver And Regulating Mind"

[Background]Tourette Syndrome（TS）is a pediatric neuropsychiatric disorder characterized by multiple motor tics and one or more vocal tics occurring at different times lasting more than one year.The disease mainly occurs in children aged 3 to 8 years,with repeated illness,prolonged course,diverse symptoms,and gradually aggravating symptoms as the age increases.Currently,about 0.3 to 0.9 percent of school-age children worldwide have TS.There are up to 2 million TS patients in China,which seriously impacts children’s physical and mental health,family,and society,and is becoming one of the common chronic severe diseases endangering children’s health.Comprehensive Behavioral Intervention（CBIT）and drugs recommended by current treatment guidelines do not fully meet the needs of patients and their guardians.The application of CBIT in China is limited,and the drug side effects and therapeutic effects in treating TS have certain limitations.Therefore,finding effective treatments that relieve patients’ symptoms is essential.Acupuncture and moxibustion,a critical traditional Chinese medicine treatment method,are widely used in treating TS.Although relevant meta-analysis studies have proved the effectiveness of acupuncture and moxibustion,the brain mechanism of the effect of acupuncture and moxibustion on TS is still blank.Functional magnetic resonance imaging Based on blood oxygenation level-dependent（BOLD）fMRI is the most commonly used method in functional magnetic resonance imaging,which is used to study brain function and understand the potential mechanism of various neurological diseases.It is a powerful tool to visualize changes in brain activity and study various neurological diseases.Based on years of clinical trials and experience in the acupuncture and moxibustion Department of our hospital,this study applied "soothing the liver and regulating the spirit" acupuncture method to treat children with TS.With an amplitude of low-frequency fluctuations（ALFF）and local low-frequency amplitude（fractional ALFF,fALFF）,the brain function changes in the treatment of TS with "soothing liver and regulating Mind" acupuncture are explored.[Aim]The first part is a case series study on improving TS clinical symptoms by "soothing liver and regulating Mind" acupuncture.The case series study aims to clarify further the effectiveness and safety of "soothing liver and regulating Mind" acupuncture in treating TS.The second part is the brain mechanism research of "soothing liver and regulating Mind"acupuncture to improve TS clinical symptoms.fMRI technology is used to preliminarily explore the brain mechanism of "soothing liver and regulating Mind" acupuncture to improve TS clinical symptoms.[Method]The first part is a case series study on improving TS clinical symptoms by "soothing liver and regulating Mind" acupuncture.Fifty-one patients with TS included in the study were treated with acupuncture 24 times for 12 weeks.Using the internationally recognized Yale Global Tic Severity Scale（YGTSS）as the primary outcome measurement tool,Combined with Clinical Global Impression（Clinical Global Impression,CGI）and Gilles de la Tourette Syndrome-Quality of Life Scale（G&S-QOL）to comprehensively evaluate the clinical efficacy of "soothing liver and regulating Mind" acupuncture in the treatment of TS.Safety evaluation and adverse events monitoring were carried out during the test.SPSS V.26.0 software was adopted.Measurement data to x-+ S,accord with normal distribution using t-test,non-normal distribution of the Mann-Whitney U rank and inspection.Paired t-test was used for intra-group comparison.Start with p<0.05 was considered statistically significant.The second part is a study on the brain mechanism of improving clinical symptoms of TS by"soothing liver and regulating Mind" acupuncture.According to the inclusion and exclusion criteria,19 children with TS were included,and 10 of them successfully completed the experiment.They were treated with the same acupuncture treatment and clinical outcome evaluation method as in the first part（once every four weeks）.At the same time,ten healthy subjects matched for age,sex,and handedness were recruited for fMRI control observation.The TS patients underwent one fMRI scan at baseline and one at the end of treatment.Healthy subjects enrolled in the study underwent only one fMRI scan.After preprocessing with MATLAB 2021b,a two-sample t-test was performed between baseline fMRI of TS patients and healthy controls to compare the differences in brain function between TS patients and healthy controls（FDR calibration,p<0.05）.Paired sample t-test（FDR calibration,p<0.05）.Image display software was Dpabi Viewer and Dpabi SulfViewer.In the statistical parameter graph,red represents increased spontaneous nerve signal,and blue represents decreased spontaneous nerve signal.Pearson correlation analysis was used to investigate the correlation between changes in brain function and clinical symptoms（YGTSS score and TTS score）in TS patients after acupuncture.p<0.05 indicated that the two indexes were correlated,and the correlation coefficient r was analyzed.[Result]1.Case series study on the improvement of TS clinical symptoms by "soothing liver and regulating Mind" acupuncture1.1 Case completion and baselineFifty-one patients with TS were collected from January 2021 to December 2022,including 46 male and 5 female children,with an average age of 9.09±2.17 years old and a first onset age of 6.74±2.03 years old.1.2 Clinical results"Soothing liver and regulating Mind" acupuncture could improve the YGTSS score,TTS score,CGI-S score,and G&S-QoL score of patients（p<0.05）,indicating that acupuncture could improve the tic symptoms,disease severity,and the quality of life of patients in aspects of compulsive dysfunction and cognitive ability.2.Study on the brain mechanism of "Soothing liver and regulating Mind" acupuncture to improve TS clinical symptoms2.1 Case completion and baselineFrom January 2021 to December 2022,19 patients with TS were finally included,among which three subjects were transferred due to head movement during data preprocessing.2mm and/or rotation>2° was excluded.Five patients fall out during treatment.Finally,ten patients with TS and ten healthy subjects were included in the analysis.All ten patients were male,with an average age of 9.25± 1.35 years old and a first onset age of 6.25±1.86 years old.2.2 Characteristics of functional brain activity in TS patientsIn the TS patients group,the ALFF signals compared with healthy controls were enhanced in the Cerebelum_Crus1_L,Supp_Motor_Area_R,Precentral_R,Cingulum_Ant_R,Cerebelum_Crus1_R;and were decreased in the Frontal_Sup_Medial_L,Frontal_Sup_L,Frontal_Mid_L,Parietal_Inf_L,Angular_L,Occipital_Mid_L,Vermis₇,Cerebelum_Crus 1_L,Cerebelum_Crus2_L,Frontal_Sup_R,Precentral_R,Parietal_Inf_R,Cerebelum_Crus1_R,Cerebelum_Crus2_R.ALFF signals were decreased in Postcentral_L,Fusiform_R,Cerebelum_Crusl_R and Cerebelum_6R after acupuncture treatment.ALFF signals in Frontal_Sup_Medial_L,Frontal_S up_L,Frontal_Mid_Orb_L,and Temporal_Inf_R was enhanced after aupuncture treatment.fALFF signals were decreased in Frontal_Sup_Orb_L,Frontal_Mid_L,Frontal_Sup_Orb_R,Frontal_Mid_Orb_R,Occipital_Mid_R,Occipital_Inf_R,Occipital_Sup_R,and Cuneus_R after acupuncture treatment.fALFF signals in Frontal_Inf_Tri_L,Cingulum_Mid_L,Cingulum_Post_R,Lingual_R,and Precuneus_R was enhanced after aupuncture treatment.In the correlation analysis,the changes of ALFF value increased in the Frontal_Mid_Orb_L and fALFF value decreased in the Frontal_Sup_Orb_R were negatively correlated with the changes of TTS score after 12 weeks of acupuncture treatment in TS patients.[Conclusion]As an exploratory study with a small sample size,a part of the brain regions with the possible effect of acupuncture（Frontal_Mid_Orb_L and Frontal_Sup_Orb_R）were obtained,and the potential brain mechanism of "soothing the liver and regulating the mind" acupuncture therapy for TS was preliminarily explored.In the future,it is necessary to carry out further randomized controlled brain mechanism studies with large samples and obtain more reliable conclusions that acupuncture can improve the clinical symptoms of TS patients by using a larger sample size and more abundant data analysis methods and analyzing the potential active brain areas,to reveal the brain mechanism of acupuncture improving TS symptoms more accurately.