The New Age of Sudomotor Function Testing: A Sensitive and Specific Biomarker for Diagnosis, Estimation of Severity, Monitoring Progression, and Regression in Response to Intervention

Abstract

Sudorimetry technology has evolved dramatically, as a rapid, non-invasive, robust, and accurate biomarker for small fibers that can easily be integrated into clinical practice. Though skin biopsy with quantitation of intraepidermal nerve fiber density is still currently recognized as the gold standard, sudorimetry may yield diagnostic information not only on autonomic dysfunction but also enhance the assessment of the small somatosensory nerves, disease detection, progression, and response to therapy. Sudorimetry can be assessed using Sudoscan™, which measures electrochemical skin conductance (ESC) of hands and feet. It is based on different electrochemical principles (reverse iontophoresis and chronoamperometry) to measure sudomotor function than prior technologies, affording it a much more practical and precise performance profile for routine clinical use with potential as a research tool. Small nerve fiber dysfunction has been found to occur early in metabolic syndrome and diabetes and may also be the only neurological manifestation in small fiber neuropathies, beneath the detection limits of traditional nerve function tests. Test results are robust, accomplished within minutes, require little technical training and no calculations, since established norms have been provided for the effects of age, gender, and ethnicity. Sudomotor testing has been greatly under-utilized in the past, restricted to specialized centers capable of handling the technically demanding and expensive technology. Yet, evaluation of autonomic and somatic nerve function has been shown to be one of the best estimates of cardiovascular risk. Evaluation of sweating has the appeal of quantifiable non-invasive determination of the integrity of the peripheral autonomic nervous system, and can now be accomplished rapidly at point of care clinics with the determination of ESC, allowing intervention for morbid complications prior to permanent structural nerve damage. We review here sudomotor function testing technology, the research evidence accumulated supporting the clinical utility of measuring ESC, the medical applications of sudorimetry now available to physicians with this device, and clinical vignettes illustrating its use in the clinical decision-making process.

Osteopontin and clusterin levels in type 2 diabetes mellitus: differential association with peripheral autonomic nerve function

“…With regard to glycemic control, sudomotor function for the hands and feet were slightly higher for those in good control but there were no statistically significant differences between the groups. Utilizing normative ESC values from the literature [8] that were defined by racial background, approximately 44% of the participants in this study had moderate to severe sudomotor dysfunction of the hands whereas approximately 20% had moderate to severe sudomotor dysfunction of the feet. It should be noted, however, that it was not possible to determine how closely the demographics of our study cohort matched the study cohorts of the published normative data.…”

“…In diabetic autonomic neuropathy, parasympathetic and/or sympathetic neurons may be affected leading to various clinical manifestations (e.g., orthostatic hypotension, hypoglycemia unawareness), including sudomotor dysfunction [7]. The examination of somatic and autonomic nerve fiber function has also been shown to be important predictors of cardiovascular risk [8]. …”

Sudomotor dysfunction as a measure of small fiber neuropathy in type 1 diabetes

“…Electrochemical skin conductance was evaluated in the T1D subjects at baseline and 12 months, and in healthy control subjects once with the SUDOSCAN device (Impeto Medical: Paris, France) as previously described (15–19; 21–24). Briefly, ESC is measured via reverse iontophoresis, an electrochemical reaction between the chlorides in sweat and stainless steel electrodes at low direct current (DC) voltage.…”

“…The current methods currently used to assess sudomotor function are expensive, time consuming, and require specialized trained personnel (12–14). The recently developed SUDOSCAN device (Impeto Medical; Paris, France) provides a simple and non-invasive method that indirectly assesses sudomotor function by measuring the electrochemical skin conductance (ESC) (15–19). This is based on the electrochemical reaction between the chloride ions in sweat and stainless steel plate electrodes on which the subject’s hands and feet are placed by combining direct current stimulation and reverse iontophoresis.…”

Tumor necrosis factor-alpha blockade with etanercept improves autonomic dysfunction in rheumatoid arthritis

“…1 It has been shown to be one of the most important predictors of cardiovascular risk. 2 However, despite the completion of half a century after the first reporting of the condition, there is no specific therapeutic strategy for autonomic dysfunction in rheumatic diseases. Therapeutic effect of diseasemodifying anti-rheumatic drugs (DMARDs) and biologic DMARDs (infliximab, tociluzimab, rituximab) on autonomic neuropathy has been demonstrated in RA and ankylosing spondylitis (AS) patients.…”