Epidermal nerve fiber density and sural nerve morphometry in peripheral neuropathies

Objective: To study intraepidermal nerve fiber (IENF) density in distal leg skin biopsies, sural nerve morphometry, electrophysiology, and clinical fe atures in patients with peripheral neuropathies. Methods: We studied 26 pat ients with neuropathic complaints who had undergone clinical evaluation, ne rve conduction studies, distal leg skin biopsy, and sural nerve biopsy. We quantified densities of IENF and of myelinated and unmyelinated fibers in t he sural nerve. Associations among skin and sural nerve morphometric measur es and sensory nerve action potential (SNAP) amplitudes were examined nonpa rametrically. Morphometric measures were examined with respect to diagnosti c category of neuropathy. Results: IENF density correlated with the densiti es of sural nerve total myelinated (r = 0.57, p = 0.0011), small myelinated (r = 0.53, p = 0.0029), and large myelinated fibers (r = 0.49, p = 0.0054) . There was a trend toward an association between IENF and sural nerve unmy elinated fiber densities (I = 0.32, p = 0.054), Sural SNAP amplitude and la rge myelinated fiber densities were highly correlated (r = 0.87, p < 0.0001 ), IENF density and sural nerve small fiber measures were concordant in 73% of patients. Reduced IENF density was the only indicator of small fiber de pletion in 23% of cases. It was usually normal in acquired demyelinating ne uropathies and where clinical suspicion for neuropathy was low. Conclusions : Distal leg Intraepidermal nerve (IENF) density may be more sensitive than sural nerve biopsy in identifying small fiber sensory neuropathies. Assess ments of IENF density and large fiber measures on biopsy and electrophysiol ogy are both useful for characterizing sensory and sensorimotor neuropathie s.