Hyperventilation during rest and exercise in orthostatic intolerance and Spiky-Leaky Syndrome, 2025, Amir Hashemizad et al

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 (VO2max). The parameters included end-tidal CO2 (ETCO2), end-tidal O2 (ETO2), 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. VO2max, 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. ETCO2 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 ETCO2 persisted throughout exercise. In contrast, ETO2 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 ETCO2 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.
LINK

 

The what now?

 

From the EDS clinic:

Spiky-Leaky Syndrome (SLS) is an emerging clinical phenomenon that links intracranial hypertension, cerebrospinal fluid (CSF) leaks, and a range of symptoms seen in hypermobility syndromes like Ehlers-Danlos Syndrome (EDS). Originally described by Dr. Andrew J. Maxwell, MD and Deborah Wardly, MD in 2024, the Spiky-Leaky Syndrome theory highlights how chronic inflammation, craniocervical instability (CCI), and environmental triggers may collectively drive this condition. Understanding SLS could pave the way for better management strategies for patients with interconnected neurological and systemic symptoms.

 

I wonder which bit is spiky?

 

This is such an interesting term. Not to be insensitive but I just couldn't resist asking AI what it thinks spiky-leaky syndrome must look like.

 

Why AI do you use?

 

Do you mean which one? Microsoft Designer

 

Haha, yeah! ME moment

 

The Complex Path to Intracranial Hypertension and CSF Leak in those with Hypermobility and Dysautonomia; The Theory of Spiky-Leaky Syndrome

"The same unstable anatomy also prevents normal CSF and lymphatic drainage thereby causing an increase in intracranial pressure (the Spiky Phase)".

"CSF pressure then pops-off through cranial nerve sheaths most notably through the olfactory nerve into sinus mucosa and into facial sinuses whereby it leaks out through the nose and ears, into facial tissue, or down the throat (the Leaky Phase)".

 

I wonder if they have actually gone looking for this CSF?