Parkinson's disease with restless legs syndrome-an in vivo corneal confocal microscopy study

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.