Accuracy of a Rapid and Non-Invasive Method for the Assessment of Small Fiber Neuropathy Based on Measurement of Electrochemical Skin Conductances.

Abstract

Peripheral nerves (PN) consist of small and large fibers (1). The small fibers represent 80% of PN and are long, thin, with little or no myelin. They are, therefore, more fragile and the first to be damaged in many pathological processes (2–5). The current clinical diagnostic methods mainly assess large fibers (6). Similarly the gold standard neurophysiological tool, namely nerve conduction studies or NCS, is also limited to measuring large fiber function. These recommended methodologies, therefore, only examine 20% of PN, those that are largest and degenerate late or not at all in certain diseases. Small fibers can be sensory or autonomic and there are several methods to assess small fiber function or structure (7). Laser-evoked potentials assess A-delta fiber function (sensory nerves) but these instruments are not widely available (8). Quantitative sensory testing (QST) measures sensitivity to cold, heat, and vibration (sensory small and large fibers) and is more widely available but time-consuming and subjective for routine clinical practice (9). Skin biopsies can assess small fiber structure but are relatively invasive (3 mm in diameter, 1 month for full healing) and, thus, are ill suited for longitudinal assessments (10). Sudomotor function assessing small fibers of the sympathetic autonomic system can be evaluated by the quantitative sudomotor axon reflex test (QSART); though considered the reference method, QSART remains mostly limited to research centers due to the technical complexity and relative discomfort of the examination (11). Other sudomotor methodologies include the Neuropad, which is semi-quantitative and not highly sensitive (12), quantitative direct and indirect testing (QDIRT) and the dynamic sweat test (DST). QDIRT and DST both induce sweating with iontophoresis of acetylcholine or pilocarpine; they are relatively tedious and not particularly suited to the outpatient clinic and there are no data validating the diagnostic utility of these newer technologies (13, 14). Specific stains can be used to evaluate sweat gland nerve fiber density (SGNFD), but there is currently no standardized methodology or normative reference ranges for SGNFD (15). The SUDOSCAN® device was developed to allow the quantitative measurement of sweat gland function using a simple and rapid process (16, 17). Results are immediately available and expressed as electrochemical skin conductances (ESCs). This technique has been compared to reference neurological tests, is not operator dependent, and could be used in the follow-up of patients and in multi-center studies (18–21). The aim of this study was to assess repeatability and reproducibility of the method in healthy volunteers (HV) and diabetic patients with a range of glycemic control.