Preoperative Evaluation,Intraoperative Local Field Potential Monitoring And Postoperative Management Of Deep Brain Stimulation In Parkinson's Disease

Part one The Study on Plasma Protein Biomarkers in Patients with Parkinson's DiseaseObjective: To investigate alterations in protein expression associated with deep brain stimulation(DBS)in an attempt to elucidate possible mechanisms of action.Methods: Plasma,obtained from three Parkinson's disease(PD)patients(pre-DBS,one month after operation before stim-on,one month after stim-on)and from three normal healthy controls,was studied for differentially expressed proteins.TMT/i TRAQ Labeling,in combination with HPLC Fractionation and LC-MS/MS Analysis,was used to identify the changed proteins(3 PD patients in different statement and 3 controls).739 proteins were identified after LC-MS/MS and protein database interrogation.Result: A total of 739 proteins were identified in this study,of which 644 contained quantitative information.If the change threshold is 1.2 times as high as t-test p-value < 0.05,Then 18 proteins were up-regulated,21 proteins were down-regulated,23 proteins were up-regulated,and 25 proteins were down-regulated in the PD3 / CK comparison group,in the p PD1 / CK comparison group,the expression of 18 proteins was up-regulated,the expression of 21 proteins was down-regulated,and the expression of 25 proteins was down-regulated in the PD3 / CK comparison group.The expression of 12 proteins was up-regulated,the expression of 12 proteins was down-regulated,the expression of 10 proteins was up-regulated in the comparison group of PD3 / PD1,and the expression of 5 proteins was down-regulated in the comparison group of PD3 / PD2.The expression of 16 proteins was up-regulated and 19 proteins were down-regulated.Conclusion: Our preliminary analysis showed that the changes of 151 protein expression levels could reveal the difference between the normal population and Parkinson's disease patients,while the changes of 56 protein expression levels might be related to deep brain stimulation therapy.Part two Quantitative Evaluation of Motor Symptoms in Patients with Parkinson's Disease----Acoustic AnalysisObjective: The aim of this study is to explore the effect of the subthalamic nucleus(STN)deep brain stimulation(DBS)on dysarthria of patients with Parkinson's Disease(PD).Methods: Ten PD patients with STN-DBS surgery participated in this experiment,and their reading speeches were collected in the state of stimulation off one month after operation(OFF),stimulation on after internal pulse generator(IPG)on for one month(ON1)and stimulation on after IPG on for three months(ON2)respectively,and all these states were under the state of medication off.Fundamental frequency(F0)contours were extracted from these speech signals and then were compared with the healthy control group(HC).Results: F0 was improved in a certain degree in the patients with STN-DBS surgical treatment.The F0 range and F0 variation of one month after operation(OFF)in the PD patients were significantly lower than those in three months(ON2),and there was no significant difference between one month after operation(OFF)and the HC group.Besides,there were no significant differences in other indicators among any other groups or states.Conclusion: STN-DBS operation can alleviate the stiffness of laryngeal muscles and vocal cords,especially in the patients whose dominant symptom is tremor and those with less motor function impairment before operation.Part three Quantitative Evaluation of Motor Symptoms in Patients with Parkinson's Disease----Bradykinesia AnalysisObjective: Bradykinesia is one of the core features of Parkinson's disease(PD)and also an important index in clinical diagnosis of PD.The quantitative assessment of motor symptoms will be helpful to diagnose PD,to monitor the progress of the disease,and to evaluate and optimize the effectiveness of antiparkinsonism drugs and other therapies.Methods: The subjects included a healthy control group and a drug therapy group.The healthy control group consisted of 15 healthy elderly people whose age and sex were matched to the drug therapy group.In the drug therapy group,11 patients with Parkinson's disease were recruited according to the Diagnostic criteria for Parkinson's disease in China(2016).The levodopa challenge tests were performed,and the drug therapy group was in two states: medication-on and medication-off state.All PD patients were assessed with the Unified Parkinson's Disease Rating Scale(UPDRS).Quantitative wearable assessment system was used to record the motion data in two groups of three paradigm maneuvers: wrist-turning,foot-tapping and walking back and forth in 10 meters.Amplitude,frequency and other motion indicators were extracted and compared among groups.Then the correlation analysis was carried out between motion data and the subitems or combination of subitems of UPDRS ?.Results: There were significant differences in wrist-turning amplitude,stride angle and turning time among the healthy control group and the drug therapy group in medication-on and medication-off state.There was a good correlation between the turning time and the scores of gait(? 29),axial symptom(? 18-19?27-31)and bradykinesia plus axial symptom(? 18?19?23-31)of UPDRS?.Conclusion: The quantitative wearable assessment system can be used to measure bradykinesia symptom in Parkinson's disease,and then to evaluate the effect of drug therapy on bradykinesia symptom in patients with Parkinson's disease,which provides a new method for accurate management of Parkinson's disease.Part four Monitoring of Field potential and Target location during Deep brain stimulation in Parkinson's DiseaseObjective: The signal characteristics of the subthalamic nucleus field potential associated with the location of the target site of DBS were dynamically detected and the optimal target of STN-DBS was found according to the law of the change of the field potential.Materials and methods: Twenty PD patients who were treated with STN-DBS were routinely used microelectrode recording to determine the surgical target during the operation,and the field potential signals were collected from 6 mm to 4 mm to 2 mm and 0 mm to the target for power spectral density analysis before and after operation.The image data were reconstructed and compared.Results: The dynamic detection of field potential by implanted electrode during DBS can reflect the relative position between the electrode and the STN nucleus,and the result of image reconstruction has good conformance with the microelectrode recording.Conclusions: DBS intraoperative field potential detection can provide a new method for target location,and guide postoperative stimulation site,parameter setting and adjustment.Part five Postoperative management of deep brain stimulation in patients with Parkinson's diseaseObjective: The aim of this study was to retrospectively analyze the therapeutic effects and residual symptoms of patients with Parkinson's disease after 3 ~ 36 months of deep brain stimulation,and disscuss the standardized and individualized management after DBS.Materials and methods: From May 2015 to February 2018,80 patients with Parkinson's disease who were treated with STN-DBS from May 2015 to February2018 were included in this study.The UPDRS,MMSE,Mo Ca,PNM,PQ39 scales were scored by the same two doctors respectively before and after DBS operation.Espacially,UPDRS ? was graded under four states of med-on/med-off and stimulator stimu-on/stimu-off.The main symptoms of Parkinson's disease,such as bradykinesia,tremor,rigidity,balance,swallowing,speech and so on,the increase and decrease of drugs,the occurrence of complications associated with stimulation,were compared and analyzed before and after DBS operation.And the optimal setting parameters and program control rules of the stimulator after operation.Summarize the best setting parameters and program control rules of postoperative stimulator program control.Results: After STN-DBS,the PQ39 scores of all patients improved significantly(P < 0.01).Motor score was significantly improved(P < 0.01),among which motor retardation,tremor and stiffness were better,speech ability was improved at the initial stage,and postural balance was not improved significantly.Cognitive,emotional improvement is not obvious.After operation,the kinds of drugs decreased by 50% and the dosage decreased by 43%(P < 0.01).The main complaints of postoperative discomfort were abnormal movement,weakness,posture and gait abnormality,disturbance of balance,abnormal sleep and constipation.Conclusions: STN-DBS is a safe and effective method for the treatment of advanced Parkinson's disease.It can improve motor symptoms well,but it is not enough to improve non-motor symptoms.Therefore,it is necessary to carry out individualized management of surgery.