We describe the clinical features, natural history, and neuropathology of 32 patients presenting with "burning feet," for whom no specific cause was identified. All had neuropathic pain in the feet and morphological abnormalities of cutaneous innervation in skin obtained using punch biopsy. Most (29) had an abnormal sensory examination. All had normal strength, proprioception, tendon reflexes, and nerve conductions. Two clinical patterns were apparent, based on natural history and spatial distribution of cutaneous denervation. Most (28) patients presented with neuropathic pain initially restricted to the feet and toes but extending more proximally to involve the legs and hands with time. Intraepidermal nerve fiber (IENF) density was most severely reduced distally, with more normal IENF densities in skin from proximal sites. In contrast, a minority (4) presented with the abrupt onset of generalized cutaneous burning pain and hyperesthesia. In these patients, IENF densities were reduced in skin from both proximal and distal sites. Absolute IENF densities in calf skin were reduced below the lower limit of normal (5th percentile) in 26 (81%). Of the 6 who underwent sural nerve biopsy, 4 had selective loss of small myelinated and/or unmyelinated axons and 2 had normal histology and fiber densities despite reduced IENF densities in skin biopsy specimens. Punch skin biopsy from proximal and distal sites is a useful means of assessing these distinctive patients and may provide further insight into pathophysiology.

Despite prominent symptoms of neuropathic pain, patients with small-fiber sensory neuropathies have few objective abnormalities on clinical examination and routine electrodiagnostic studies. We quantified intraepidermal nerve fiber (IENF) density in sections of skin obtained by punch skin biopsy, and found it to be significantly reduced in patients with painful sensory neuropathies compared with age-matched control subjects. In addition, IENF density correlated with clinical estimates of neuropathy severity, as judged by the extent of clinically identifiable sensory abnormalities. IENF density at the calf was lower than that obtained from skin at more proximal sites, indicating the length dependency of small-fiber loss in these neuropathies.

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CNS demyelination is not a previously reported feature of acquired copper deficiency. The authors report two patients with idiopathic hypocupremia and hyperzincemia, hematologic changes of copper deficiency, and extensive CNS demyelination. Hematologic recovery followed copper supplementation, both initially and after relapse off copper therapy, while serum zinc levels remained high and the neurologic abnormalities only stabilized.

This evidence-based review was performed to evaluate the utility of nerve conduction studies (NCSs) and needle electromyography (EMG) in the diagnosis of tibial neuropathy at the ankle (tarsal tunnel syndrome, TTS). A total of 317 articles on TTS were identified that were published in English from 1965 through April 2002, from the National Library of Medicine MEDLINE database. All articles were reviewed on the basis of six selection criteria. The results of this search revealed that four articles met five or more criteria. All four articles examined the use of electrodiagnostic (EDX) techniques for the evaluation of patients with clinically suspected TTS, and were included in this practice parameter. Each of these four studies was considered to meet Class III level of evidence. NCSs were abnormal in some patients with suspected TTS. Sensory NCSs were more likely to be abnormal than motor NCSs but the actual sensitivity and specificity could not be determined. The sensitivity of needle EMG abnormalities could not be determined. NCSs may be useful for confirming the diagnosis of tibial neuropathy at the ankle, recommendation Level C. Well-designed studies are needed to evaluate more definitively EDX techniques in TTS.