Abstract
Cutaneous nerves represent the most distal part of the sensory nervous system. We took advantage of the good discernibility of longitudinal myelinated fibers in skin biopsies to analyze the distribution of nodal and paranodal proteins in neuropathies and to assess nodal disorganization as a diagnostic marker of demyelinating neuropathy (NP). We analyzed myelinated nerve fibers in skin biopsies from the finger and the proximal leg of 52 prospectively recruited patients with different peripheral neuropathies and 17 controls. We performed immunohistochemical double labeling with anti-MBP, anti-PGP9.5, anti-caspr, anti-pan-neurofascin, and anti-pan-sodium-channel. Three potential features of demyelinating NP could be established: elongated nodes of Ranvier and dispersion of contactin-associated protein (caspr) staining were found more often in demyelinating than in axonal neuropathies (p < 0.05) and were not detectable in normal controls. Broadening of neurofascin staining was detectable more often in demyelinating neuropathies compared with normal controls (p < 0.05). Our data suggest that pathological changes of nodal architecture can be visualized in skin biopsies and that the detection of elongated nodes of Ranvier and alterations in the distribution of paranodal proteins may be useful in the diagnostic assessment of peripheral NP.
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