Structural and functional small fiber abnormalities in the neuropathic postural tachycardia syndrome.

Christopher H Gibbons,Adam Benson,Roy Freeman,Istvan Bonyhay,Ningshan Wang,Pedro Gonzalez-Alegre

doi:10.1371/journal.pone.0084716

Christopher H Gibbons, Adam Benson + Show 4 more

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https://doi.org/10.1371/journal.pone.0084716

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Journal: PloS one	Publication Date: Dec 27, 2013
Citations: 116	License type: CC BY 4.0

Affiliation: Beth Israel Deaconess Medical Center, Harvard University

Abstract

ObjectiveTo define the neuropathology, clinical phenotype, autonomic physiology and differentiating features in individuals with neuropathic and non-neuropathic postural tachycardia syndrome (POTS).MethodsTwenty-four subjects with POTS and 10 healthy control subjects had skin biopsy analysis of intra-epidermal nerve fiber density (IENFD), quantitative sensory testing (QST) and autonomic testing. Subjects completed quality of life, fatigue and disability questionnaires. Subjects were divided into neuropathic and non-neuropathic POTS, defined by abnormal IENFD and abnormal small fiber and sudomotor function. ResultsNine of 24 subjects had neuropathic POTS and had significantly lower resting and tilted heart rates; reduced parasympathetic function; and lower phase 4 valsalva maneuver overshoot compared with those with non-neuropathic POTS (P<0.05). Neuropathic POTS subjects also had less anxiety and depression and greater overall self-perceived health-related quality of life scores than non-neuropathic POTS subjects. A sub-group of POTS patients (cholinergic POTS) had abnormal proximal sudomotor function and symptoms that suggest gastrointestinal and genitourinary parasympathetic nervous system dysfunction. Conclusions and RelevancePOTS subtypes may be distinguished using small fiber and autonomic structural and functional criteria. Patients with non-neuropathic POTS have greater anxiety, greater depression and lower health-related quality of life scores compared to those with neuropathic POTS. These findings suggest different pathophysiological processes underlie the postural tachycardia in neuropathic and non-neuropathic POTS patients. The findings have implications for the therapeutic interventions to treat this disorder.

Highlights

The postural orthostatic tachycardia syndrome (POTS) is defined by an excessive increase in heart rate in the upright position with associated symptoms of orthostatic intolerance [1]
A total of 8 of 24 individuals had sudomotor dysfunction based on quantitative direct and indirect sudomotor testing (QDIRT) abnormalities (Figure 1)
We report the first comprehensive analysis of the symptoms, neurophysiology and cutaneous neuropathology of individuals with neuropathic and nonneuropathic POTS

Summary

Introduction

The postural orthostatic tachycardia syndrome (POTS) is defined by an excessive increase in heart rate in the upright position with associated symptoms of orthostatic intolerance [1]. Several lines of evidence point to a restricted peripheral neuropathy, sympathetic denervation predominantly in the lower hemibody, as a cause of POTS in some individuals. The evidence includes reports of venous denervation [3], impaired distal sudomotor function [4,5], lower norepinephrine spillover in the legs than the arms [6], and the association with denervation on skin biopsy [7]. This condition is known as neuropathic POTS. In tertiary referral center studies, a neuropathic etiology underlies POTS in 33 to 50% of individuals [6,8]

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