Abstract
Autonomic and somatic denervation is well established in Parkinson's disease (PD). Objectives(1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. MethodsTwenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease – autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III “ON”] and cumulative Levodopa dose. ResultsPD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. ConclusionCCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD.
Highlights
Parkinson's disease (PD) is a neurodegenerative disease recognized clinically by its motor symptoms of rest tremor, bradykinesia, rigidity and postural instability
Corneal Nerve Fiber Density (CNFD): The number of main nerves per square millimetre, Corneal Nerve Branch Density (CNBD): The number of branches emanating from each main nerve per square millimetre and Corneal Nerve Fiber Length (CNFL): The length of all nerve fibers and branches were quantified and the mean derived from the right and left eye for each parameter
corneal nerve fiber density (CNFD), intraepidermal nerve fiber density (IENFD) and neuropathy disability score (NDS) were independent of vitamin B12, folate, methylmalonate and homocysteine levels. This is the first study to systematically characterize corneal nerve changes in PD using the non-invasive technique of corneal confocal microscopy
Summary
Parkinson's disease (PD) is a neurodegenerative disease recognized clinically by its motor symptoms of rest tremor, bradykinesia, rigidity and postural instability. The motor syndrome results from degeneration of dopaminergic neurons in the substantia nigra. Abnormal aggregates of alpha-synuclein in neuronal cells form the histopathological hallmark of PD. L. Kass-Iliyya et al / Parkinsonism and Related Disorders 21 (2015) 1454e1460 the central nervous system. Phosphorylated alpha-synuclein deposits have been demonstrated in the autonomic nerves of the colon, cardiac plexus and more recently cutaneous C fibers [1e5]
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