Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure?

Background. 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 aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods. The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results. Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. 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.

Detecting nocturnal hypertension in Parkinson's disease and multiple system atrophy: proposal of a decision-support algorithm.

A pathological nocturnal blood pressure (BP) profile, either non-dipping or reverse dipping, occurs in more than 50% of subjects diagnosed with multiple system atrophy (MSA) or Parkinson's disease (PD). This may play a negative prognostic role in α-synucleinopathies, but, being mostly asymptomatic, remains largely underdiagnosed. In this proof-of-concept study, we aimed at developing a decision-support algorithm to predict pathological nocturnal BP profiles during a standard tilt-table examination in PD and MSA. Sixteen MSA and 16 PD patients underwent standard tilt-table examination and 24-h ambulatory BP monitoring (24-h ABPM). Clinical and tilt test differences between patients with a normal and a pathological nocturnal BP profile at 24-h ABPM were assessed, and a decision-support algorithm was developed accordingly. 75% of MSA and 31 % of PD patients showed a pathological nocturnal BP profile. This was associated with more pronounced orthostatic BP drop (p = 0.03), joint occurrence of orthostatic hypotension and supine hypertension (p = 0.046), and lack of BP overshoot in the late phase II (II_L, p = 0.002) and in the phase IV (p = 0.007) of the Valsalva manoeuvre. Combined ∆BP ≤0.5 mmHg in the II_L and ≤-7 mmHg in the IV phase of Valsalva manoeuvre correctly predicted a pathological nocturnal BP profile with 87.5% sensitivity and 85.7% specificity. Pathological nocturnal BP profiles are associated with evidence of cardiovascular noradrenergic failure in PD and MSA. The Valsalva manoeuvre is routinely performed during standard tilt-table examinations. We propose the naked-eye evaluation of Valsalva phase II_L and phase IV BP behaviour as time-sparing screening tool for pathological nocturnal BP profiles in PD and MSA.