Validity of clinical small-fiber sensory testing to detect small-nerve fiber degeneration

BACKGROUND: Small-nerve fiber, or small-fiber, degeneration commonly occurs in patients with peripheral neuropathies, resulting in a deterioration of nerve function. Currently, the gold standard to identify small-fiber degeneration is through skin biopsy. Simple clinical tests aim to identify small-fiber degeneration, but their validity remains unknown. OBJECTIVES: To examine the validity of clinical tests to assess small-nerve fiber degeneration, using carpal tunnel syndrome as a model neuropathy. METHODS: One hundred seven participants (22 healthy, 85 with carpal tunnel syndrome) in this prospective, cross-sectional diagnostic accuracy study underwent pinprick testing of the index finger and were assessed for cold detection threshold and warm detection threshold using quantitative sensory testing. In a subgroup of patients with carpal tunnel syndrome (n = 51), cold and warm sensations were also tested, using coins at room and body temperature, respectively. The validity of these clinical tests was established against intra-epidermal nerve fiber density measured in skin biopsies from the index finger. RESULTS: Optimal validity occurred with clusters of tests. Specifically, normal warm or cold sensation is highly sensitive to rule out small-fiber degeneration (sensitivity, 0.98; 95% confidence interval [CI]: 0.85, 0.99), but has a low specificity (0.20; 95% CI: 0.03, 0.52). By contrast, a reduction in pinprick is highly specific (0.88; 95% CI: 0.72, 0.95), and so can be used to rule in small-fiber degeneration. For quantitative sensory testing, the highest specificity (0.83) occurs for warm detection threshold and the highest sensitivity (0.84; 95% CI: 0.72, 0.91) for cold detection threshold or warm detection threshold. CONCLUSION: Pinprick testing, followed by warm and cold tests if pinprick is normal, is a valid and cost-effective method to detect small-fiber degeneration. For quantitative sensory testing, warm detection threshold is useful for ruling in small-fiber degeneration. To rule out small-fiber degeneration, both cold detection threshold and warm detection threshold must be negative.