Structural and Functional Small Fiber Abnormalities in the Neuropathic Postural Tachycardia Syndrome

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.

Small‐fiber neuropathy with cardiac denervation in postural tachycardia syndrome

“…Nevertheless, most of the nerve fiber density values considered abnormal in our study were only slightly below the normal range. Results of a recent study on a smaller group of POTS patients demonstrated that about half (9 of 20) had mildly reduced IENF, which is in line with the results obtained from our larger cohort.…”

Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review

“…Gibbons and Freeman [25] defined neuropathic POTS as a reduced intra-epidermal nerve fiber density through skin biopsies with impaired sensory or sudomotor function. It is noteworthy that there is not concordance between the different markers of autonomic neuropathy (abnormal skin biopsies, sudomotor testing or quantitative sensory analyses) in the same patient.…”

Postural Tachycardia Syndrome: Beyond Orthostatic Intolerance

“…Norepinephrine spillover is not a practical clinical test. A thermoregulatory sweat test or a Quantitative Sudomotor Axon Reflex Test (QSART), quantitative sensory testing, or a skin biopsy can also be used to determine whether an autonomic neuropathy exists [44;25]. …”