Parkinson’s disease with restless legs syndrome—an in vivo corneal confocal microscopy study

Abstract

Small fiber neuropathy (SFN) has been suggested as a trigger of restless legs syndrome (RLS). An increased prevalence of peripheral neuropathy has been demonstrated in Parkinson’s disease (PD). We aimed to investigate, in a cross-sectional manner, whether SFN is overrepresented in PD patients with concurrent RLS relative to PD patients without RLS, using in vivo corneal confocal microscopy (IVCCM) and quantitative sensory testing (QST) as part of small fiber assessment. Study participants comprised of age- and sex-matched PD patients with (n = 21) and without RLS (n = 21), and controls (n = 13). Diagnosis of RLS was consolidated with the sensory suggested immobilization test. Assessments included nerve conduction studies (NCS), Utah Early Neuropathy Scale (UENS), QST, and IVCCM, with automated determination of corneal nerve fiber length (CNFL) and branch density (CNBD) from wide-area mosaics of the subbasal nerve plexus. Plasma neurofilament light (p-NfL) was determined as a measure of axonal degeneration. No significant differences were found between groups when comparing CNFL (p = 0.81), CNBD (p = 0.92), NCS (p = 0.82), and QST (minimum p = 0.54). UENS scores, however, differed significantly (p = 0.001), with post-hoc pairwise testing revealing higher scores in both PD groups relative to controls (p = 0.018 and p = 0.001). Analysis of all PD patients (n = 42) revealed a correlation between the duration of l-dopa therapy and CNBD (ρ = −0.36, p = 0.022), and p-NfL correlated with UENS (ρ = 0.35, p = 0.026) and NCS (ρ = −0.51, p = 0.001). Small and large fiber neuropathy do not appear to be associated with RLS in PD. Whether peripheral small and/or large fiber pathology associates with central neurodegeneration in PD merits further longitudinal studies.

Wide-field mosaics of the corneal subbasal nerve plexus in Parkinson’s disease using in vivo confocal microscopy

“…Study design, participants, inclusion and exclusion criteria. The initial study from which the raw IVCM data was collected 30 had a cross-sectional design, where participants were enrolled in the period from Spring 2018 to Autumn 2019 at the outpatient clinic at Center for Neurology and Karolinska University Hospital, Stockholm, Sweden. The study encompassed control participants without PD, and PD patients with (PD + RLS) and without RLS (PD-RLS) matched for age and sex.…”

“…nr 2018/264-31/2 (2019-03158)). Inclusion and exclusion criteria have been previously described in detail 30 .…”

“…Here we present an IVCM dataset representing a larger number of patients (n = 42) compared to prior IVCM studies of PD. The raw data in this dataset was originally used 30 to investigate a possible relationship between the presence of RLS in PD and corneal nerve parameters. Here we provide an entire dataset of high quality wide-field mosaics of the corneal SBNP in PD patients (21 with and 21 without RLS) and 13 age-matched controls.…”

Semiautomated and Automated Quantitative Analysis of Corneal Sub-Basal Nerves in Patients With DED With Ocular Pain Using IVCM

“…A total of 50 voluntary participants were enrolled in this study, comprising 25 patients with DED with ocular pain (7 men and 18 women, mean age: 43.8 ± 14.7 years) and 25 mm/5' , and average corneal staining score of 1.89 ± 1.59. These indicators were within normal limits in the healthy controls.…”

Real-time large-area imaging of the corneal subbasal nerve plexus

“…With its lateral resolution, in vivo corneal confocal microscopy (CCM) is the current state of the art technique for obtaining high-quality images of the subbasal nerve plexus (SNP) at the epithelial basement membrane 1 , 2 . Using this technology, the morphology of the SNP has been studied as a conveniently accessible biomarker in various conditions such as dry eye disease 3 , diabetic neuropathy 4 , 5 , chemotherapy 6 , HIV infection 7 , and Parkinson’s disease 8 . However, the inhomogeneity of the local distribution of SNP nerve structures limits the sensitivity and specificity of this method, particularly regarding the relatively small field of view of the available instruments in the order of only 0.10–0.16 mm 2 .…”