Parasympathetic and Sympathetic Monitoring Identifies Earliest Signs of Autonomic Neuropathy

The progression of autonomic dysfunction from peripheral autonomic neuropathy (PAN) to cardiovascular autonomic neuropathy, including diabetic autonomic neuropathy and advanced autonomic dysfunction, increases morbidity and mortality risks. PAN is the earliest stage of autonomic neuropathy. It typically involves small fiber disorder and often is an early component. Small fiber disorder (SFD) is an inflammation of the C-nerve fibers. Currently, the most universally utilized diagnostic test for SFD as an indicator of PAN is galvanic skin response (GSR), as it is less invasive than skin biopsy. It is important to correlate a patient’s symptoms with several autonomic diagnostic tests so as not to treat patients with normal findings unnecessarily. At a large suburban northeastern United States (Sicklerville, NJ) autonomic clinic, 340 consecutive patients were tested with parasympathetic and sympathetic (P&S) monitoring (P&S Monitor 4.0; Physio PS, Inc., Atlanta, GA, USA) with cardiorespiratory analyses, and TMFlow (Omron Corp., Hoffman Estates, Chicago, IL, USA) with LD Technology sudomotor test (SweatC™). This is a prospective, nonrandomized, observational, population study. All patients were less than 60 y/o and were consecutively tested, analyzed and followed from February 2018 through May 2020. P&S Monitoring is based on cardiorespiratory analyses and SweatC™ sudomotor testing is based on GSR. Overall, regardless of the stage of autonomic neuropathy, SweatC™ and P&S Monitoring are in concordance for 306/340 (90.0%) of patients from this cohort. The result is an 89.4% negative predictive value of any P&S disorder if the sudomotor GSR test is negative and a positive predictive value of 90.4% if the sudomotor testing is positive. In detecting early stages of autonomic neuropathy, P&S Monitoring was equivalent to sudomotor testing with high sensitivity and specificity and high negative and positive predictive values. Therefore, either testing modality may be used to risk stratify patients with suspected autonomic dysfunction, including the earliest stages of PAN and SFD. Moreover, when these testing modalities were normal, their high negative predictive values aid in excluding an underlying autonomic nervous system dysfunction.