title: Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome.
abstract: OBJECTIVE
  Many non-musculoskeletal complaints in EDS-HT may be related to dysautonomia. This study therefore aims to investigate whether dysautonomia is present and to explore the underlying mechanisms.
  
  
  METHODS
  A total of 39 females with EDS-HT and 35 age-matched controls underwent autonomic function testing. Resting autonomic tone was assessed using heart rate variability (frequency domain) and baroreflex sensitivity analysis (cross correlation). Autonomic reactivity was assessed using the Autonomic Reflex Screen test battery. Factors suspected to contribute to dysautonomia, e.g., neuropathy, medication use, decreased physical activity, depression, pain-induced sympathetic arousal, and connective tissue laxity, were quantified using validated questionnaires, the Beighton score, and measurement of skin extensibility.
  
  
  RESULTS
  The EDS-HT group showed autonomic deregulation with increased sympathetic activity at rest and reduced sympathetic reactivity to stimuli. Increased resting activity was indicated by a higher LF/HF ratio compared to controls (1.7 ± 1.23 vs 0.9 ± 0.75, p = 0.002); decreased reactivity by a greater BP fall during valsalva (-19 ± 12 vs -8 ± 10, p < 0.001), and a smaller initial diastolic BP increase during tilt (7% vs 14%, p = 0.032). Orthostatic intolerance was significantly more prevalent in EDS-HT than controls (74% vs 34%) and was most frequently expressed as postural orthostatic tachycardia. Lowered QSART responses suggest that sympathetic neurogenic dysfunction is common in patients (p < 0.013), which may explain the dysautonomia in EDS-HT. Further, connective tissue laxity and vasoactive medication use were identified as important factors in aggravating dysautonomia (p < 0.035).
  
  
  CONCLUSIONS
  Dysautonomia consisting of cardiovascular and sudomotor dysfunction is present in EDS-HT. Neuropathy, connective tissue laxity, and vasoactive medication probably play a role in its development.
authors: Department of Rehabilitation Sciences and Physiotherapy, Ghent University, Artevelde University College, De Pintelaan 185, 1B3, 9000 Ghent, Belgium. Electronic address: inge.dewandele@ugent.be.
authors: Inge
authors: I
authors: De Wandele
authors: Department of Rehabilitation Sciences and Physiotherapy, Ghent University, Artevelde University College, De Pintelaan 185, 1B3, 9000 Ghent, Belgium.
authors: Lies
authors: L
authors: Rombaut
authors: Department of Basic Medical Sciences, Physiology Group, Ghent University, Ghent, Belgium.
authors: Luc
authors: L
authors: Leybaert
authors: Hypertension Clinic, Erasme Hospital, Brussels, Belgium.
authors: Philippe
authors: P
authors: Van de Borne
authors: Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
authors: Tine
authors: T
authors: De Backer
authors: Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Fransiska
authors: F
authors: Malfait
authors: Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Anne
authors: A
authors: De Paepe
authors: Department of Rehabilitation Sciences and Physiotherapy, Ghent University, Artevelde University College, De Pintelaan 185, 1B3, 9000 Ghent, Belgium.
authors: Patrick
authors: P
authors: Calders
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000502:physiology*; D004535:Ehlers-Danlos Syndrome / Q000150:complications* / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D054969:Primary Dysautonomias / Q000150:complications* / Q000503:physiopathology; D011795:Surveys and Questionnaires
keywords: Autonomic dysfunction; Ehlers–Danlos syndrome; Hypermobility; Orthostatic intolerance