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

Abstract

Objective: To define the neuropathology, clinical phenotype, autonomic physiology and differentiating features in individuals with neuropathic and non-neuropathic postural tachycardia syndrome (POTS).

Methods: Twenty-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.

Results: Nine 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 relevance: POTS 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.

Figure 1. Distribution of test results.

Abnormal results are displayed within the lightly shaded region. The 9 individuals that meet criteria for neuropathic POTS (abnormal skin biopsy and 1 other abnormal test) are in the darkly shaded region. A total of 9 subjects had abnormal intra-epidermal nerve fiber density (skin biopsy). A total of 12 individuals had abnormal quantitative sensory testing (QST). A total of 8 individuals had abnormal sudomotor (QDIRT) testing. * = individuals with neuropathic POTS, ^† = individuals with cholinergic POTS.

Figure 2. Results of European Quality of Life Questionnaire.

A. The EuroQol VAS for self-perceived healthy-related quality of life (Score of 100 = best imaginable health state, 0= worst imaginable health state). The non-neuropathic POTS had the lowest perceived quality of life, while the neuropathic POTS subjects had lower self-perceived health than control subjects. * p< 0.01 vs. controls, † p<0.01 vs. neuropathic POTS (ANOVA with Tamhanes T2 post-hoc test). The EuroQol 5D (B) shows the individual sub-dimensions with the percent of individuals reporting abnormalities shown. Significant differences in mobility, usual activities and pain were noted between groups (*=P<0.05, Fishers exact test). A greater percent of non-neuropathic POTS subjects reported self-perceived difficulty across all sub-dimensions than control and neuropathic POTS subjects (with the exception of anxiety which was reported with the same frequency as neuropathic POTS subjects).