Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure? – Biomed Res Int. – Feb 2017 – free full-text PMC article
Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by
- generalized joint hypermobility,
- skin texture abnormalities, and
- visceral and vascular dysfunctions,
- also comprising symptoms of autonomic dysfunction.
This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests.
This work confirmed a common perturbation of autonomic regulation of the cardiovascular function in adults with JHS/EDS-HT. POTS (Postural orthostatic tachycardia syndrome) and OI (orthostatic intolerance) were the more commonly observed profiles at HUT, while OH, as a genuine form of autonomic failure, was rare in our sample.
Interestingly, we observed a difficulty in completing both the handgrip test and the Valsalva maneuver among the JHS/EDS-HT patients.
It is possible that the hand problems related to fatigue and joint pain or instability (so commonly observed in JHS/EDS-HT), as well as the lack of proprioception, might have contributed to this pathological outcome.
During the Valsalva maneuver, we registered [various technical measurements] as expected in physiological peripheral sympathetic vasoconstriction.
The recent finding of small fiber neuropathy as a common finding in EDS, also comprising JHS/EDS-HT, is an intriguing conundrum in light of our findings. In fact, the presence of small fiber neuropathy could identify a clinical subgroup of POTS (a.k.a. “neuropathic” POTS).
Considering the results obtained with the HUT(Head-up tilt)-test, we found POTS in ~50% JHS/EDS-HT patients and a high rate of OI in accordance with previous studies
POTS (Postural orthostatic tachycardia syndrome) and OI (Orthostatic intolerance) have been frequently described in chronic fatigue syndrome and fibromyalgia, a fact that suggests that these conditions may share deconditioning. Deconditioning could then operate in concert with “somatic hypervigilance” to lead to a disturbing mismatch between physiological responses and perception in some individuals
Accordingly, it seems reasonable that exercise-based rehabilitation may be effective in the medium- and long-term treatment of POTS and related conditions with deconditioning  [I found this hard to believe, so I checked the reference -zyp]
Reference: 30. Joyner M. J., Masuki S. POTS versus deconditioning: the same or different? Clinical Autonomic Research. 2008;18(6):300–307. doi: 10.1007/s10286-008-0487-7.[PMC free article]
In fact, it has been demonstrated that, during acute exercise, POTS patients have excessive increases in BP and reduced stroke volume at absolute workload compared to sedentary controls without intrinsic abnormality of HR regulation. In addition, cardiac remodeling and blood volume expansion associated with exercise training increase physical fitness and improve performance in these patients  [I found this hard to believe, so I checked the reference -zyp]
Reference: 31. Fu Q., Levine B. D. Exercise in the postural orthostatic tachycardia syndrome. Autonomic Neuroscience: Basic and Clinical. 2015;188:86–89. doi: 10.1016/j.autneu.2014.11.008.[PMC free article]
In response to orthostatic stimulation, we observed comparable changes in the HR markers of sympathetic activation and parasympathetic withdrawal in both groups.
An interesting finding of our study is that the BRS (baroreflex sensitivity) of JHS/EDS-HT patients, at rest, is significantly higher than controls and this difference is more marked in the subgroup of patients with POTS.
Different hypothesis can explain the BRS variations.
- The resting HR seems to be influenced by exercise. Different studies have demonstrated reduction of intrinsic HR induced by long-term competitive training in athletes compared with sedentary individuals
- Another possible mechanism to explain the abnormalities of BRS in JHS/EDS-HT may be linked to the reduction of artery stiffness in the elderly
From this perspective, it should be possible to speculate that the modification of the connective tissue which characterizes JHS/EDS-HT may modify vessels compliance and should explain the differences observed in the baroreflex function.
BP: Blood pressure bpm: Beats per minute BRS: Baroreflex sensitivity DBP: Diastolic blood pressure ECG: Electrocardiogram EDS: Ehlers-Danlos syndrome EDS-HT: Ehlers-Danlos syndrome, hypermobility type HF: High-frequency HR: Heart rate HRV: Heart rate variability HUT: Head-up tilt JHS: Joint hypermobility syndrome LF: Low-frequency LF/HF: Low-frequency/high-frequency ratio n.u.: Normalized units OH: Orthostatic hypotension OI: Orthostatic intolerance POTS: Postural orthostatic tachycardia syndrome SBP: Systolic blood pressure VR: Valsalva ratio.