Accuracy Of Levodopa Challenge Test For Parkinson’s Disease Diagnosis And Differential Diagnosis

Background and Objective:Parkinson’s disease(PD)is a chronic progressive disabling neurodegenerative disorder and is common in the elderly.The pathological characteristics of PD is the presence of depigmentation and neuronal loss in substantia nigra,together with intraneuronal inclusions or Lewy bodies.Its clinical mainly symptoms include bradykinesia,the resting tremor,rigidity and postural unsteadiness,usually companied with olfactory disorder,constipation,sleep disorders,cognitive disorders,depression and other non-motor symptoms.Now there is no clear treatment can effectively delay the occurrence and development of the disease,more cannot be cured.In the last stage not only the symptoms of the disease increased,there will be drugs caused by motor and non-motor complications,seriously affecting the patients’ quality of life and work ability.Therefore,the early diagnosis and timely intervention on PD patients are particularly important for drug efficacy,quality of life and prognosis.Given patients levodopa in order to take dopamine uptake,so that patients’ motor symptoms improved significantly.However,the pathogenesis of VP,PSP,MSA,DLB,CBD,ET are different with PD,so the effect of levodopa of non-PD patients is uncertain or invalid.Patients with dopaminergic responsiveness contribute to the early diagnosis and differential diagnosis of PD,and also predict the efficacy of sustained Long-Term Levodopa Response.At present,acute levodopa challenge test is used to assess dopaminergic responsiveness,and have the same effect with the chronic challenge test.,but less studies at home.Now there is still a lack of uniform test method,drug dose,assessment criteria,the cut-off point and so on,so the sensitivity and specificity of the test there are some differences and influence the accuracy of the assessment.The establishment of standardized acute levodopa challenge test and the assessment of dopaminergic responsiveness are great importance to the diagnosis of PD.In this study,the levodopa challenge test was improved to make patients in the short term to achieve more effective dopaminergic responsiveness and to enhance the accuracy of the test.And further explore the factors affecting the results of the test,in order to reduce the false negative and false positive.In addiiton,depth understanding of the impact of dopaminergic responsiveness on patients with PD and non-PD Parkinson’s syndrome provides the possibility of differential diagnosis.It could provide the important evidence of early detection,diagnosis,treatment and prognosis.Methods:Continuous screening from September 2015 to March 2016 in the Zhengzhou University First Affiliated Hospital of 90 patients with Parkinsonism’s motor symptoms were included in the levodopa challenge test.To collect all the basic information of patients,including gender,age,course of disease,onset age,H&Y grade,the time of dopamine treatment and so on.Before the test,all patients were routinely treated with blood routine test,electrolyte,liver and kidney function,electrocardiogram(ECG),MRI or CT and other related checks.An improved levodopa test was used in this study,specific test methods are:1.Patients in 72 hours disable dopamine receptor agonists,24 hours disable levodopa and other anti-PD drugs;2.Before taking the Unified Parkinson’s Disease Rating Scale(UPDRS)motor section improved,score in the "off" period;3.Oral Madopar 125 mg four times a day(respectively,at 6: 00,10: 00,14: 00,18: 00),and 1 hour before meals or 1 hour and a half hours after meals;4.From the medication started to monitor blood pressure,heart rate and other discomfort,if no adverse reactions,the continuous medication for 7 days;5.After 7 days of medication,the UPDRS motor section score improvement was measured;6.Improvement rate =(baseline score before medication-lowest score after medication)/ baseline score before taking medication × 100%,a minimal 30% of improvement on UPDRS motor section scores were positive;7.According to UPDRS motor section improvement rate is divided into two groups: <30% group,≥ 30% group.After one year of follow-up,85 patients were followed up.And they were divided into PD group had 60 cases and non-PD group had 25 cases with MDS clinical diagnostic criteria for Parkinson’s disease in 2015.The ROC curve of the levodopa challenge test was calculated using the UPDRS part Ⅲimprovement rate as a diagnostic index.Kappa analysis was performed to verify the consistency of the trial with clinical follow-up.To analysis the difference between the improvement rate <30% group and the≥30% group of PD patients and of non-PD patients.And the multivariate logistic regression was used to analysis the independent influencing factors of false positive and false negative results.Results:1.The accuracy of levodopa challenge test on PD diagnosis: The ROC curve was established for the levodopa challenge test,the area under the ROC curve is 0.85.The cut-off point was set at 32.5%,and overall sensitivity and specificity of the test to predict clinical diagnosis of PD was 86.7% and 76.0%,positive predictive ratio was 88.1%,negative predictive ratio was 69.2%.The accuracy of diagnosis of PD is high.The Kappa value of the test and the follow-up diagnosis was 0.58,the consistency was statistically significant(P<0.001).2.The Response of PD patients to levodopa challenge test: The test had 52(86.7%)true positive cases and 8(13.3%)false negative cases.PD patients with UPDRS PartIII score improvement rate <30% had a longer course of disease,lower H & Y grade and longer dopamine treatment than the improved rate of ≥30% group(P <0.05).The lighter the disease and the longer time of dopamine preparation,the lower improvement rate and less obvious the reaction.3.The Response of non-PD patients to levodopa challenge test :18(72%)true negative cases occurred in 4 VP,4 ET,2 MSA,2 CBD,2 DLB,1 PSP and three had no definitive diagnosis.7(28%)false positive cases occurred in 2 VP,2 MSA,2 PSP and 1 CBD.Non-PD patients with UPDRS PartIII score improvement rate ≥30% had a shorter course of disease,higher H & Y grade than the improved rate of <30% group(P <0.05).Non-PD Patients in the early stage with levodopa challenge test may have a certain reactivity.The longer course of disease,the reaction is less obvious.Conclusions:1.The PD patients of milder clinical symptoms and long time of dopamine treatment have poor response of levodopa challenge test.2.The Response of non-PD patients to levodopa challenge test is related to the course of disease.The early stage of VP,MSA,PSP and CBD have a certain effect on dopaminergic responsiveness.