Small-fiber neuropathy with cardiac denervation in postural tachycardia syndrome

Muscle Nerve. 2014 Dec;50(6):956-61. doi: 10.1002/mus.24245. Epub 2014 Aug 29.


Introduction: Postural tachycardia syndrome (POTS) is a disorder of orthostatic intolerance characterized by excessive tachycardia of unknown etiology. Our objective in this study was to evaluate the correlation between C-fiber involvement as shown by skin biopsy and adrenergic cardiac metaiodobenzylguanadine (MIBG) uptake in POTS patients.

Methods: Skin biopsies of 84 patients with POTS were examined by Protein Gene Product 9.5 (PGP9.5) immunohistochemistry and were compared with MIBG myocardial scintigraphy imaging data.

Results: Mean intraepidermal nerve fiber (IENF) density was in the lower normal age-adjusted range, 7.2 ± 2.9/mm (normal ≥ 7/mm), and was slightly below the normal range in 45% of POTS patients. MIBG uptake was reduced in 21% of patients. Low IENF density correlated with reduced cardiac MIBG uptake (r = 0.39, P = 0.001).

Conclusions: A subset of neuropathic POTS patients may harbor mild small fiber neuropathy with abnormalities of unmyelinated nerve fibers in the skin associated with reduced myocardial postganglionic sympathetic innervation.

Keywords: autonomic disorder; cardiac denervation; orthostatic intolerance; postural tachycardia syndrome; small fiber neuropathy.

Publication types

  • Comparative Study

MeSH terms

  • 3-Iodobenzylguanidine / metabolism
  • Adolescent
  • Adult
  • Biopsy
  • Cohort Studies
  • Comorbidity
  • Erythromelalgia / diagnosis*
  • Erythromelalgia / epidemiology
  • Erythromelalgia / pathology*
  • Female
  • Heart / diagnostic imaging
  • Heart / innervation*
  • Humans
  • Incidence
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology
  • Nerve Degeneration / diagnosis*
  • Nerve Degeneration / epidemiology
  • Nerve Degeneration / pathology*
  • Nerve Fibers, Unmyelinated / pathology
  • Postural Orthostatic Tachycardia Syndrome / complications*
  • Postural Orthostatic Tachycardia Syndrome / pathology
  • Retrospective Studies
  • Skin / innervation
  • Skin / pathology
  • Tomography, Emission-Computed, Single-Photon
  • Young Adult


  • 3-Iodobenzylguanidine