Syndrome Characteristics Of Parkinson's Disease And Clinical Observation Of Shengqing Jiangzhuo Recipe

Objective:To study the characteristics of traditional Chinese medicine(TCM)syndrome element of Parkinson’s disease(PD)and explore the correlations of syndrome elements,motor symptoms and biological indicators in plasma based on the objective diagnosis of PD-PES.Another,to observe the preliminary efficacy of method for ascending lucidity and descending turbidity in the treatment of PD and provide reference for the treatment of PD by Chinese medicine.Methods:The first and second parts of this study was conducted by a multi-center clinical investigation method,a cohort of 358 PD patients were enrolled from Dongzhimen Hospital,Beijing Hospital and Peking University Third Hospital.In the first part,all subjects were conducted Unified Parkinson’s disease Rating Scale(UPDRS)assessment,quantitative diagnosis and expert diagnosis of TCM syndromes elements.The diagnostic properties of a pattern element scale for PD(PD-PES)were measured by receiver-operator characteristic curves(ROC).The parallel validity was assessed by multiple linear regression analysis.Internal consistency was computed by Cronbach’s alpha.In the second part,358 patients were divided into early stage(H&Y 1-2,n=157),mid-term(H&Y 2.5-3,n=168)and advanced stage(H&Y 4,n=33)according to the modified Hoehn&Yahr stage.TCM syndrome elements of three groups discriminated by PD-PES were compared,and correlations of syndrome elements,UPDRS and Aβ40、Aβ42、T-tau in plasma were analyzed by multiple linear regression analysis.The third part was carried out by a multi-center randomized,double-blind,placebo-controlled design,in order to observe the preliminary efficacy of formula of ascending lucidity and descending turbidity in the treatment of 73 PD patients.The observation group and placebo group were treated with Chinese herbal formule or placebo formule based on the conventional therapy,respectively.The research included a 2-week placebo run-in period and a 12-week treatment period.By intentionality(ITT)and Per Protocol Set(PPS)analysis,the changes in scores of UPDRS,constipation severity instrument(CSI),Parkinson’s Disease Sleep Scale(PDSS),Hamilton Depression Scale(HAMD),and Parkinson’s disease questionnaire with 39-items(PDQ-39)were compared between the two groups.Results:1.The Area Under the Curve(AUC)for each subscale in PD-PES was above 0.75.When the cut-off score was set at 7,the kidney deficiency,blood deficiency and phlegm muddiness subscale had good specificities(87.5-94.6%)but poor sensitivities(41.0-67.9%);sensitivity(75.0-95.1%)and specificity(70.7-97.1%)of other subscales were good.The Cronbach’s alpha for PD-PES was 0.724.The scores of marrow deficiency,liver wind and Qi deficiency had correlation with UPDRS,UPDRS-Ⅱ,UPDRS-Ⅲ and H&Y stage(P<0.05);the scores of kidney deficiency,Qi deficiency and Yang hyperactivity had correlation with UPDRS-I(P<0.01);Yin deficiency had correlation with UPDRS-IV(P<0.01).2.The most common TCM pattern elements of PD were marrow deficiency,liver wind and Qi deficiency,and the frequencies of them were 67.9%,55.3%and 50.8%,respectively.Comparing with groups of mid-term and advanced stage,the scores of marrow deficiency(P<0.001,P<0.001)and kidney deficiency(P<0.001,P=0.038)were lower in early stage.The scores of Qi deficiency in groups of early stage and mid-term were lower than advanced stage(P=0.007,P=0.040).Multi-pattern element in mid-term and advanced stage were more than early stage(P=0.010,P=0.003).The scores of marrow deficiency,liver wind and Qi deficiency had positive correlation with UPDRS,UPDRS-Ⅲ(P<0.001).There was positive correlation between scores of liver wind with temor symptom(r=0.094,P<0.001).And scores of marrow deficiency and blood deficiency were positively correlated with rigidity symptom(r=0.045,P<0.001;r=0.038,P=0.023).The scores of marrow deficiency,liver wind and Qi deficiency had positive correlation with bradykinesia(r=0.205,P<0.001;r=0.191,P<0.001;r=0.159,P=0.001).The scores of marrow deficiency and Qi deficiency had postive relation with abnormal posture and gait(r=0.242,P<0.001;r=0.133,P=0.003).3.By ITT-LOCF and PPS analysis,there were no signidicant differences on improvement of UPDRS and CSI scores between treatment group and placebo group(P>0.05).Regarding to the subscales of UPDRS and CSI,the changes of UPDRS-IV scores in treatment group were significantly better than placebo group at week 4 and week 8(PITT=0.012,PITT =0.024).Within group comparison showed that the UPDRS total scores were significantly improvement from baseline in treatment group at week 4 and week 8(PITT=0.033,PPPS=0.047;PITT=0.025,PPPS=0.020).Between group comparison showed that the PDSS score change of treatment group was significantly better than placebo group at week 4(PITT=0.006,Ppps=0.004),and the PDQ-39 score change of treatment group was significantly better than placebo group at week 12(PITT=0.048,Ppps=0.040).In the process of the trial,there were 7 cases of AEs(9.6%),and no SAEs.No statitical difference were found in incidence of AEs between treatment group and placebo group(P=0.860).Conclusions:1.PD-PES has a good diagnostic performance.When the cut-off score was set at 7,the subscales have good sensitivity and specificity,except for kidney deficiency,blood deficiency and phlegm muddiness subscales.PD-PES is suitable for discriminating the pattern subtypes in PD patients.2.The marrow deficiency,liver wind and Qi deficiency pattern elements are significantly correlation with PD but influenced by the severity of the disease.And the more severe of the condition,the higher frequency of complex syndromes.3.Formula of ascending lucidity and descending turbidity may improve the living ability and sleep conditions of PD patients.