Identification of corneal and intra-epidermal axonal swellings in amyotrophic lateral sclerosis.

Introduction/aims: In patients with amyotrophic lateral sclerosis (ALS), axonal spheroids in motor axons have been identified in post-mortem studies. In this study, axonal spheroids and swellings on C-fibers of ALS patients were investigated using corneal confocal microscopy (CCM) and skin biopsy, respectively.

Methods: Thirty-one ALS patients and 20 healthy subjects were evaluated with CCM to assess corneal nerve-fiber length (CNFL), -fiber density (CNFD), -branch density (CNBD), dendritic cell (DC) density, and axonal spheroids originating from C-fibers (>100 μm ). In addition, intraepidermal nerve fiber density (IENFD) and axonal swellings (>1.5 μm) were assessed in skin biopsies obtained from the arms and legs of 22 patients and 17 controls.

Results: In ALS patients, IENFD, CNFD, CNFL, and CNBD were not different from controls. The density of DCs and the number of patients with increased DC density were higher in ALS patients than controls (p = .0005 and p = .008). The number of patients with axonal spheroids was higher than controls (p = .03).

Discussion: Evaluation of DCs and axonal bulbs in C-fibers of ALS patients could provide insights into pathophysiology or potentially serve as biomarkers in ALS.