Excessive Hypocapnic Cerebral Vasoconstriction in [hEDS] Assessed With Real‐Time [MRI] During Lower‐Body Negative Pressure, 2026, Gerlach+

[SNT Gatchaman]

Excessive Hypocapnic Cerebral Vasoconstriction in Hypermobile Ehlers–Danlos Syndrome Assessed With Real‐Time Magnetic Resonance Imaging During Lower‐Body Negative Pressure
Darius A Gerlach; Anja Bach; Laura de Boni; Fiona Fischer; Tatjana Barth; Alex Hoff; Jorge Manuel; Jens Jordan; Andrea Maier; Jens Tank

BACKGROUND
Orthostatic intolerance is common in hypermobile Ehlers–Danlos syndrome (hEDS) with one third of patients fulfilling postural orthostatic tachycardia syndrome criteria. Our aim was to assess cerebral blood flow in patients with hEDS and postural orthostatic tachycardia syndrome during orthostasis, which may be responsible for orthostatic intolerance.

METHODS
In 18 individuals with hEDS and postural orthostatic tachycardia syndrome and 20 healthy controls, we conducted real‐time phase contrast magnetic resonance imaging of the middle cerebral artery with and without an orthostatic challenge through 30 mm Hg lower‐body negative pressure.

RESULTS
During lower‐body negative pressure, heart rate increased more in hEDS than in controls (15.0±8.3 bpm versus 7.8±7.7 bpm, P=0.009); blood pressure remained unchanged; middle cerebral artery flow per heartbeat decreased more in hEDS (−28%±16% versus −15%±13% in controls, P=0.013) with decreased mean volumetric flow in hEDS (−12%±17%, P<0.001 versus −6%±8% in controls, P=0.102); average middle cerebral artery peak blood flow velocity decreased in both groups (hEDS: 44.6±8.1 cm/s to 37.6±8.4 cm/s, P<0.001; controls: 40.3±10.9 cm/s to 36.9±11.1 cm/s, P=0.018); respiration rate increased in hEDS (14.3±5.1/min to 17.4±5.3/min, P=0.002) leading to a decrease in end‐tidal CO2 (39.2±4.2 mm Hg to 35.6±6.4 mm Hg, P=0.025), and cerebrovascular resistance increased more in hEDS (50.8%±48.4%, P<0.001) versus (20.3%±20.6%, P=0.005) in controls.

CONCLUSIONS
Individuals with hEDS and postural orthostatic tachycardia syndrome maintain cerebral perfusion primarily through tachycardic compensation during orthostatic stress despite hypocapnic vasoconstriction.

REGISTRATION
DRKS00028279

Web | DOI | PDF | Journal of the American Heart Association | Open Access

 

[Utsikt]

Participants were chosen on the basis of international criteria (Beighton Scoring System),14 with skin biopsy testing to exclude other Ehlers–Danlos syndrome subtypes and autonomic testing confirming POTS through a tilt‐table test, where clinical symptoms were observed during the first 10 minutes of standing in orthostasis, along with an increase in heart rate of at least 30 bpm or a tachycardia >120 bpm.15 Clinical information on comorbidities, current medication, and symptom severity are reported in Table S1.

What does the hEDS label add to the POTS?

 

[SNT Gatchaman]

Yes it's likely a distraction. In the discussion they say —

This study has several limitations: The study cohort was limited to patients with hEDS who also met POTS criteria. The addition of patients with POTS only would have permitted teasing out hEDS-specific responses in cerebrovascular regulation.

I think we can probably ignore hEDS (and save Jo a comment ) and assume that the findings here would be the same in anyone meeting the same POTS criteria. That may be incorrect of course.

Here are some summary quotes —

We recruited 18 individuals with hEDS and POTS (13 women; age, 31.8±6.6 years; 22.4±4.4 kg/m2 ) and 20 matched healthy controls (12 women; age, 34.7±10.2 years; 25.0±3 kg/m2).

We placed participants in an MRI scanner […] with the lower part of the body in an MRI-compatible LBNP device that was sealed at the iliac crest. Following 20 minutes of rest with 0 mmHg LBNP, we obtained the first real-time phase contrast MRI […] After 9 minutes at −30 mmHg LBNP, we obtained the second MRI.

We measured bilateral middle cerebral artery (MCA) flow with real-time phase contrast sequences 16 for 32 seconds […] We recorded ECG, respiration rate, and end-tidal CO2 (ETCO2 ) and measured brachial blood pressure […]

We calculated cerebrovascular resistance as mean blood pressure divided by flow per beat and defined cerebrovascular reactivity as the change in MCA flow per beat divided by the change in ETCO2 : (ΔCBF/ΔETCO2).

Significance threshold was P<0.05 with Bonferroni.

Our key finding is that individuals with hEDS and POTS exhibit a marked reduction in MCA flow per heartbeat during orthostatic stress, which tachycardia only partially compensates. Despite preserved arterial pressure, overall CBF declines, indicating incomplete hemodynamic compensation. Thus, patients rely on tachycardia to stabilize brain perfusion, yet this mechanism does not fully offset flow reductions in the presence of hypocapnia and increased cerebrovascular resistance.

Previous studies using transcranial Doppler showed substantial reductions in CBF velocities during head-up tilt in POTS. Our study extends these observations by quantifying absolute flow and showing that reductions in velocity alone may underestimate cerebral hypoperfusion when vessel diameter changes.

The observed decrease in MCA cross-sectional area during LBNP supports dynamic vascular behavior rather than a fixed vessel caliber.

The increase in cerebrovascular resistance, together with the reduction in MCA flow, indicates that cerebral perfusion becomes more constrained during orthostatic stress in hEDS with POTS. […] the concomitant increase in respiratory rate and decrease in ETCO2 suggest that hypocapnia contributed to cerebral vasoconstriction. However, our data do not establish causality, and hypocapnia may either drive or result from reduced cerebral perfusion.

The combination of reduced flow, increased resistance, and hypocapnia suggests that normal cerebral flow regulation is challenged during orthostatic stress. Rather than indicating a primary failure of autoregulation, these findings are consistent with a shift toward CO2-mediated vascular control under conditions of central hypovolemia and altered ventilation.