Participants

Twenty-eight patients with idiopathic PD who received regular follow-up at the movement disorder clinic of National Taiwan University Hospital (NTUH) were enrolled in the study. The inclusion criteria were fulfillment of the diagnosis of PD based on the United Kingdom PD Society Brain Bank clinical diagnostic criteria¹⁹ and an absence of sustained sensory symptoms, neuropathic pain, or weakness in the limbs. We excluded patients who had systemic medical illnesses, such as diabetes mellitus, chronic liver, and kidney diseases, malignancy, endocrine diseases, autoimmune diseases, alcoholism, toxic exposure, or a family history of neuropathy. None of the patients had clinically relevant signs of autonomic dysfunction and mutations in Parkin, PINK1, LRRK2, SCA2, and SCA3 were previously excluded.^20,21 All patients were treated with L-dopa or a combination with dopamine agonists and had good clinical responses. L-dopa equivalents were calculated according to Möller et al.²² We defined the daily L-dopa dose as the average daily dosage of L-dopa in the 6 months before entering the study. We also collected the total cumulative dose of L-dopa equivalents in the year prior to enrollment. Each patient was examined using the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS part III) and Hoehn-and-Yahr staging. Patients maintained their regular anti-PD medications and were examined while in the on status. Twenty-three age- and gender-matched healthy subjects were enrolled for direct comparisons of the results of skin biopsy and CHEP.

Our study was approved by the Ethics Committee of NTUH (201106076RB) and followed the Helsinki Declaration regarding international clinical research involving humans. Written informed consent was obtained from each participant before enrollment in the study.