Abstract

Background

Orthostatic intolerance, with or without postural orthostatic tachycardia syndrome (POTS), is collectively referred to as orthostatic intolerance dysautonomia syndromes (OIDS). This condition often presents with daytime hyperventilation, which is considered to be secondary to sympathetic hyperactivity. This hyperventilation appears to be a key characteristic in a newly described subset of patients with OIDS who also exhibit craniocervical instability, mast cell activation syndrome (MCAS), hypermobility spectrum disorder (HSD), and the phenomenon of alternating intracranial hypertension with hypotension due to cerebrospinal fluid (CSF) leaks, collectively termed Spiky-Leaky Syndrome (SLS).

Methods

We performed a retrospective review of clinical metabolic exercise data in young patients with SLS, comparing them to matched patients with OIDS and healthy controls (CTL). We assessed metabolic parameters at rest, at the anaerobic threshold (AT), and at maximal oxygen consumption (VOmax). The parameters included end-tidal CO (ETCO), end-tidal O (ETO), peak oxygen pulse, total work performed, and peak oxygen uptake efficiency slope (OUESp).

Results

Of 323 reviewed exercise stress tests, 44 were conducted on patients with SLS, 210 on those with OIDS, and 53 on healthy controls. VOmax, AT, peak oxygen pulse, total work performed, and OUESp were all significantly reduced in patients with OIDS and were further reduced in those with SLS. ETCO levels were notably lower at rest, at the time of the anaerobic threshold, and at the time of maximal oxygen uptake in the OIDS group, and even more so in the SLS group. These lower levels of ETCO persisted throughout exercise. In contrast, ETO demonstrated a similarly strong but opposite trend.

Conclusion

Compared to the control group, patients with OIDS-and especially those with SLS-exhibited reduced metabolic parameters, particularly a decrease in peak oxygen pulse and ETCO levels during both rest and exercise. These findings suggest a reduction in ventricular preload and chronic daytime hyperventilation. These exercise parameters may serve as markers for POTS physiology and sympathetic hyperactivity, both of which could play a role in the pathophysiology of SLS.

MeSH

Exercise, Physiology, Hyperventilation, Orthostatic Intolerance, Primary Dysautonomias, Work, Anaerobic Threshold, Pulse, Mast Cell Activation Syndrome