Parkinson's disease is characterized by different clinical subtypes but the pathophysiological mechanisms underlying the clinical subtypes are unknown. The aim of the present study is to provide the first neurophysiological, neuroradiological and neurobiological characterization of PD clinical subtypes. A further aim of the study will be to identify the neurophysiological correlates of the various types of PD tremor (rest, re-emergent and postural). For this project 150 patients with PD will be enrolled. For each patient we will collect demographic and clinical data. The clinical variables will include motor as well non-motor symptoms. PD clinical subtypes will be identified by using a `data-driven¿ cluster analysis of patients based on clinical and demographic featuires . For the neurophysiological assessment motor and sensory functions weill be investigated. For the assessement of primary motor cortex excitability and plasticity we will use different single pulse and repetitive transcranial magnetic stimulation (TMS) techniques. To test motor performance, we will measure the kinematic parameters of index finger abductions performed with maximum velocity. Sensory function and sensorimotor investigations will be assessed with somatosensory temporal discrimination threshold (STDT) at rest and during voluntary finger movements . All patients will undergo a magnetic brain resonance imaging standardized scan. In order to provide a neurobiological profile of PD subtypes we will also measure a-synuclein concentration in the saliva of patients with PD. Finally the neurophysiological correlates of the different types of tremor will use the recent developed technique of TMS-electroencephalogram.
The present study will allow to understand whether the various subtypes in PD rae due to different pathophysiological mechanisms and to provide useful biomarkers for PD subtype.