Several authors have described the presence of different clinical subtypes in Parkinson's disease (PD). However, the pathophysiological basis of PD clinical subtypes are poorly understood. The aim of the present study is to provide the first neurophysiological characterization of PD clinical subtypes. We will enroll 100 patients with PD and 100 age- and sex-matched healthy controls. We will collect the PD patients' demographic and clinical data. The clinical variables will include motor as well as non-motor symptoms. In order to identify PD clinical subtypes, we will use the demographic and clinical variables to perform a data-driven cluster analysis. Several neurophysiological tools will be used to investigate motor and sensory functions in PD patients and healthy controls. In order to assess primary motor cortex excitability and plasticity we will use different single pulse and repetitive transcranial magnetic techniques. To test motor performance, we will measure the kinematic parameters of index finger abductions. To investigate sensory function we will measure the somatosensory temporal discrimination threshold (STDT). The sensorimotor integration mechanisms will be investigated by assessing the effect of voluntary movement on STDT
The present study will allow to clarify whether the presence of various subtypes in PD is restricted to the clinical features or reflects the involvement of different pathophysiological mechanisms.
In 2014, the National Institutes of Health delineated subtype identification as one of the top 3 clinical research priorities in PD (Siebner et al., 2014). The clinical definition of subtypes, however, does not allow to understand the pathophysiology of PD subtypes. In the present study, we will provide, for the first time, a comprehensive neurophysiological characterization of PD clinical subtypes. By using this approach we will identify the pathophysiological features of PD subtypes, and we will demonstrate that PD subtypes are not only clinically different but have different pathophysiological mechanisms.
The results of the present might represent a major step toward developing new clinical trials and new opportunities for personalized medicine to treat PD.