Abstract
Background: Previous studies have shown cutaneous small fiber pathology in patients with Parkinson's disease (PD). These studies have focused on nerve degeneration, but recent reports suggest that nerve regeneration may also be important in PD pathology.Objective: To establish the extent of intraepidermal nerve fiber (IENF) degeneration and regeneration and its relationship to clinical and neurological deficits in Parkinson's disease (PD).Methods: Twenty-three PD patients and 10 age-matched controls underwent skin biopsy and assessment of somatic and autonomic symptoms and deficits. We have assessed Intraepidermal Nerve Fiber Density (IENFD) using standard PGP9.5 staining and GAP-43 to assess Mean Axonal Length (MAL) and Intraepidermal Total Nerve Fiber Length (IETNFL).Results: IENFD (p < 0.0001), MAL (p < 0.0001), IETNFL/Area (p = 0.009), and IETNFL/Length (p = 0.04) were significantly reduced in patients with PD compared to controls. IENFD correlated significantly with disease duration (p = 0.03), cumulative levodopa dose (p = 0.02), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (p = 0.01), Schwab and England Activities of Daily Living (ADL) (p = 0.03), NSP (p = 0.03), and 30:15 ratio (p = 0.03). IETNFL/Area correlated with the Autonomic Scale for Outcomes in Parkinson's Disease (SCOPA-AUT) (p = 0.03) and Diabetic Neuropathy Symptom score (DNS) (p = 0.04) and IETNFL/Length correlated with DNS (p = 0.03). MAL correlated with SCOPA-AUT (p = 0.01), DNS (p = 0.02), and DB-HRV (p = 0.02).Conclusion: Increased IENF degeneration and impaired regeneration correlates with somatic and autonomic symptoms and deficits in patients with PD.
Highlights
Parkinson’s disease (PD) affects the central, and the peripheral nervous system [1]
intraepidermal nerve fiber density (IENFD) (p < 0.0001), Mean Axonal Length (MAL) (p < 0.0001), Intraepidermal Total Nerve Fiber Length (IETNFL)/Area (p = 0.009), and IETNFL/Length (p = 0.04) were significantly reduced in patients with PD compared to controls
IETNFL/Area correlated with the Autonomic Scale for Outcomes in Parkinson’s Disease (SCOPA-AUT) (p = 0.03) and Diabetic Neuropathy Symptom score (DNS) (p = 0.04) and IETNFL/Length correlated with DNS (p = 0.03)
Summary
Parkinson’s disease (PD) affects the central, and the peripheral nervous system [1]. Peripheral neuropathy (PN) has been reported in 55% of patients with idiopathic PD [2] and a recent systematic review has shown that 56.9% have biopsy proven small fiber neuropathy [3, 4]. Wang et al have reported that α-synuclein deposition is increased in cutaneous sympathetic but not in sensory nerve fibers [3]. Previous studies have shown cutaneous small fiber pathology in patients with Parkinson’s disease (PD). These studies have focused on nerve degeneration, but recent reports suggest that nerve regeneration may be important in PD pathology
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