Analysis of myelinated fibers in human skin biopsies of patients with neuropathies

Given the availability of effective but costly treatment for acquired demyelinating neuropathies, biomarkers for these disorders are urgently needed. Here we aimed to quantify morphological abnormalities of myelinated fibers in skin biopsies from the proximal leg of patients with neuropathies to determine a potential diagnostic role of this method. We used double immunofluorescence to detect myelinated and unmyelinated fibers in thigh skin from 81 patients with polyneuropathy, 19 patients with small fiber neuropathy, and 25 controls. Dermal myelinated fibers were reduced 6.8-fold in patients with polyneuropathy (p < 0.0001). The number of dermal nerve bundles with myelinated fibers was reduced 2.7-fold (p = 0.0025). In small fiber neuropathy, myelinated fibers in dermal nerve bundles were only reduced in the length-dependent type, indicating that this subgroup may represent an early stage of generalized polyneuropathy. Elongated nodes of Ranvier were detectable in demyelinating neuropathies only. Our data suggest that changes in the number and morphology of myelinated fibers in the proximal leg can confirm the diagnosis of neuropathy, and may help to distinguish between demyelinating and axonal neuropathy, and to differentiate pure small fiber neuropathy from early polyneuropathy.