The Pathophysiological Correlates of Parkinson's Disease Clinical Subtypes.

Background: Possible pathophysiological mechanisms underlying Parkinson's disease (PD) clinical subtypes are unknown. The objective of this study was to identify pathophysiological substrate of PD subtypes using neurophysiological techniques.

Methods: One hundred de novo PD patients participated. We collected patient demographic and clinical data, which were used to perform a hierarchical cluster analysis. The neurophysiological assessment tested primary motor cortex excitability and plasticity using transcranial magnetic stimulation. To evaluate motor performance, we performed a kinematic analysis of fast index finger abduction. To investigate sensory function and sensorimotor mechanisms, we measured the somatosensory temporal discrimination threshold at rest and during movement, respectively.

Results: Hierarchical cluster analysis identified 2 clinical clusters. Cluster I ("mild motor-predominant") included patients who had milder motor and nonmotor symptoms severity than cluster II patients, who had a combination of severe motor and nonmotor manifestations (diffuse malignant). We observed that the diffuse malignant subtype had increased cortical excitability and reduced plasticity compared with the mild motor-predominant subtype. Kinematic analysis of motor performance demonstrated that the diffuse malignant subtype was significantly slower than the mild motor-predominant subtype. Conversely, we did not observe any significant differences in sensory function or sensorimotor integration between the two PD subtypes.

Conclusions: De novo PD subtypes showed different patterns of motor system dysfunction, whereas sensory function and sensorimotor integration mechanisms did not differ between subtypes. Our findings suggest that the subtyping of PD patients is not a mere clinical classification but reflects different pathophysiological mechanisms. Neurophysiological parameters may represent promising biomarkers to evaluate PD subtypes and their progression. © 2020 International Parkinson and Movement Disorder Society.