Small fiber pathology in patients with periodic limb movement during sleep

Objective: Periodic leg movements during sleep (PLMS) characterize a common movement disorder occurring at nighttime in comorbidity with several neurological conditions. Its pathogenesis is still a puzzling issue. We aimed at exploring the presence of small fiber pathology (SFP) in patients with PLMS. Methods: We examined skin punch biopsies from the distal and proximal sites in 22 patients with periodic limb movement disorder (PLMD) (17 males, with a mean age of 58.50 ± 13.3), without predisposing causes for peripheral neuropathy, and 20 age- and sex-matched healthy controls (HCs), quantifying Epidermal Nerve Fibre Density (ENFD) and phosphorylated-alpha-synuclein (p-α-syn) deposits. Results: ENFD was significantly decreased at the leg sites in patients compared to HCs (6.52 ± 3.01 fibers/mm vs 13.02 ± 2.76 fibers/mm; p < 0.0001), while a comparable density of fibres was found at the cervical site (18.88 ± 5.92 fibers/mm vs 20.81 ± 10.35 fibers/mm; p = 0.56). Percentages of innervation in the legs in patients with PLMD positively correlated with total sleep time (r = 0.648) and sleep efficiency (r = 0.558) during nocturnal polysomnography. Analysis of p-α-syn deposition was negative in both groups. Conclusions: Small fibre pathology is present in a subgroup of patients with PLMS. Whether SFP might be an additional risk factor for triggering the onset of PLMS or could foster PLMS severity remains to be elucidated.