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From the Department of Neurology (Dr. Herrmann), University of Rochester, NY; and Departments of Neurology (P. Hauer and Drs. Griffin, Cornblath, and McArthur), Neuroscience (Dr. Griffin), and Epidemiology (Dr. McArthur), Johns Hopkins University, Baltimore, MD.
Address correspondence and reprint requests to Dr. D.N. Herrmann, Department of Neurology, University of Rochester, SMH 601 Elmwood Avenue, Box 673, Rochester, NY 14642; e-mail: David_Herrmann{at}urmc.rochester.edu
OBJECTIVE: To study intraepidermal nerve fiber (IENF) density in distal leg skin biopsies, sural nerve morphometry, electrophysiology, and clinical features in patients with peripheral neuropathies.
METHODS: We studied 26 patients with neuropathic complaints who had undergone clinical evaluation, nerve conduction studies, distal leg skin biopsy, and sural nerve biopsy. We quantified densities of IENF and of myelinated and unmyelinated fibers in the sural nerve. Associations among skin and sural nerve morphometric measures and sensory nerve action potential (SNAP) amplitudes were examined nonparametrically. Morphometric measures were examined with respect to diagnostic category of neuropathy.
RESULTS: IENF density correlated with the densities 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 unmyelinated fiber densities (r = 0.32, p = 0.054). Sural SNAP amplitude and large 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 depletion in 23% of cases. It was usually normal in acquired demyelinating neuropathies 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. Assessments of IENF density and large fiber measures on biopsy and electrophysiology are both useful for characterizing sensory and sensorimotor neuropathies.
Key words: Intraepidermal nerve fiber density—Skin biopsy—Sural nerve morphometry—Sural nerve biopsy—Electrophysiology—Peripheral neuropathy.
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