Exploring Physiological Biomarkers of Parkinsonism with Hyperkinetic Symptoms

The diagnosis and management of Parkinson’s disease have been significantly improved in the past decade. However, less research achievement has been reached in other kinds of parkinsonism. In the past few years, we have focused our research on dystonia and PD with and without levodopa-induced dyskinesia. Based on our recent success, we are here being interested in studying the pathophysiology of the diseases that commonly present a mixture of clinical symptoms with parkinsonism and hyperkinesias (e.g. dystonia and dyskinesia). Among the diseases, we have selected corticobasal syndrome, Parkinson’s disease carrying parkin gene and dopa-responsive dystonia for the current project to study. By comparing and contrasting the three representative diseases with different degrees of parkinsonism and dystonia/dyskinesia, we can further understand their underlying pathophysiology. Moreover, the results may provide physiological biomarkers that are helpful for the diagnosis and future research of the diseases. Subjects have to come for at least 3 sessions of experiments to test their motor cortical plasticity and reversibility, the connectivity between the premotor and primary motor cortices, short-interval intracortical inhibition (SICI) recruitment, brainstem blink reflex recovery cycle and spinal reciprocal inhibition in the forearm. SICI recruitment will be measured before and after plasticity is induced. Patients may have to come with 24-hour drug withdrawal or reduced dose of levodopa. Patients with DRD will be asked to come for 3 experiments in both medication on and off conditions to have 6 experiments in total. Each experiment will be performed at least 1 week apart from each other in a pseudo randomised order to avoid carryover effects. In addition, the experiments need to arrange according to patients’ available time slots. Hence, we estimate that three years are required for completing the whole study. To our knowledge, there has been no relevant study published so far. Many of the parameters in the current study are based on our novel techniques and results published recently. These parameters show distinguishing features on Parkinson’s disease and dystonia. We therefore expect to provide further understandings in the underlying mechanism and to discover the unique presentation of each disease in the aspect of physiology through this study. Although genetic tests are available for some forms of DRD and parkin-associated PD, these unique physiological presentations may contribute as biomarkers to improve the accuracy of diagnosis. Moreover, the biomarker may be used for monitoring the disease progress and therapeutic effects.

Project ID:PC10301-0553
External Project ID:NSC102-2314-B182-030-MY3