Small fiber pathology in patients with periodic limb movement during sleep

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.

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.

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.

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.