Contact Heat-Evoked Potential Stimulation for the Evaluation of Small Nerve Fiber Function

Background: Small fiber peripheral neuropathy (SFN) is emerging as a common complication in diabetes. Currently there are few, not easily available methods of determining the integrity of small nerve fibers. This study was designed to determine the utility of a noninvasive technique, contact heat-evoked potential stimulation (CHEPS), on the identification of SFN and compare it with standardized measures of diabetic peripheral neuropathy (DPN). Subjects and Methods: We evaluated 31 healthy controls and 30 participants with type 2 diabetes and DPN using neurologic examination, nerve conduction studies (NCS), autonomic function tests, quantitative sensory tests (QSTs), and CHEPS. Contact heat was administered to the thenar eminence, volar and dorsal forearms, lower back, and distal lower limb. Evoked potentials were recorded from the skull vertex. Latencies and amplitudes were determined. Results: Intrapeak amplitude (IA) values were significantly reduced in the DPN group at the lower back (44.93 +/- 6.5 vs. 23.87 +/- 3.36 mu V; P < 0.01), lower leg (15.87 +/- 1.99 vs. 11.68 +/- 1.21 mu V; P < 0.05), and dorsal forearm (29.89 +/- 8.86 vs. 14.96 +/- 1.61 mu V; P < 0.05). Pooled data from both groups showed that IA values at different sites significantly correlated with clinical neurologic scores, NCS, QSTs, and autonomic function. Receiver operator characteristic curve analysis, used to evaluate the performance of CHEPS in detecting nerve dysfunction, was most significant for IA at the lower back (area under the curve, 0.778; +/- SE, 0.06; 95% confidence interval, 0.654-0.875; P < 0.0001). Conclusions: This study suggests that CHEPS is a novel, noninvasive technique able to detect impairment of small nerve fiber function from skin to cerebral cortex, providing an objective measure of C and A delta nerve dysfunction.