Epidermal nerve fiber density in sensory ganglionopathies : Clinical and neurophysiologic correlations

We assessed the involvement of somatic unmyelinated fibers in sensory ganglionopathies by skin biopsy and quantitative sensory testing (QST). Sixteen patients with ganglionopathy, 16 with axonal neuropathy, and 15 normal controls underwent skin biopsy at the proximal thigh and the distal leg. Intraepidermal nerve fibers (IENF) were immunostained by anti-protein gene product 9.5, and their linear density was quantified under light microscopy. Confocal microscopy studies with double staining of nerve fibers and basement membrane were also performed. Healthy subjects and neuropathy patients showed the typical proximodistal gradient of IENF density; in neuropathies, values were significantly lower at the distal site of the leg, confirming the length-dependent loss of cutaneous innervation. Conversely, ganglionopathy patients with hyperalgesic symptoms did not show any change of IENF density between the proximal thigh and the distal leg. The distinct pattern of epidermal denervation seen in sensory ganglionopathy reflected the degeneration of somatic unmyelinated fibers in a fashion that was not length-dependent, which was consistent with both clinical and neurophysiologic observations and supported the diagnosis.