Upright Head Pressure in POTS and Long COVID: Understanding a Common but Overlooked Symptom

Simplified Overview condensed from Exelby & Hill, 2025,  “Upright Head Pressure in Long COVID- from Acute Neurovascular Injury to Chronic Hypoxic Support Failure: a Mechanistic Hypothesis”

Dr Graham Exelby & Michelle Hill (Certified Vodder Therapist)

What it feels like

Many patients describe a sensation of pressure building in the head when standing, walking, or sitting upright.  It may feel like:

• “My head is going to burst.”

• “There’s a balloon inflating inside my skull.”

• “My head feels clearer when I lie down.”

This is usually accompanied by blurred or tunnel vision, that may be postural, brain fog, light and sound sensitivity, dizziness, palpitations or sweating from autonomic dysregulation.  This often improves when lying flat, during sleep, or after gentle lymphatic massage.

Common triggers/aggravating factors include:

• Heat, exertion, or stress.

• Large meals or alcohol (blood pooling + mast cell activation).

• Hormonal changes (menstrual cycle, perimenopause).

• Weather/barometric shifts, long flights.

• Long periods of neck flexion (phone/laptop slouch).

What’s likely going on

This is not “migraine” or “anxiety.” It is a real, physiological response caused by pressure imbalances and fluid stagnation in the brain due to:

• Neurovascular unit (NVU) dysfunction — including pericyte and astrocyte failure- where it all starts, where the SARS-CoV-2 affects the pericytes

• Low-grade inflammation and vascular stiffness, COVID causes persistent endothelial dysfunction, microclots and reduced brain blood flow with physical changes to areas in the brain seen on MRI brain Neuroquant, and perfusion changes in brain SPECT scans that reflect perfusion changes where the functional changes reflect the accompanying symptoms.

• Dysfunctional fascia/ connective tissue, aggravated by underlying problems especially EDS.  Ongoing low-grade hypoxia and inflammation remodel connective tissues around the neck and skull base.  weakened ligaments/fascia in the upper neck allow intermittent venous congestion and altered CSF dynamics, especially when upright

• Venous obstruction/congestion, especially in the internal jugular and vertebral veins so there is increased venous backflow pressure.  Collateral veins may enlarge (especially at the back of the neck), but lymphatic collaterals do not form → bottlenecks remain.

• Glymphatic failure — the brain’s cleaning system isn't working properly, aggravated by the pressure increase in the venous system in the brain, which then requires an increase in CSF pressure to simply have the valves between the 2 system able to function (arachnoid granulations often larger as the body attempts to accommodate this)

• Net result- Poor drainage of cerebrospinal fluid (CSF)

• Hypoxia in brainstem- this then causes dysregulation in the autonomic nervous system as the regulatory region in the paraventricular nucleus is affected, and the hypoxic locus coeruleus responds as well increasing nor-adrenaline in the brain and further effects on the glymphatic and arterial flow.

Scientific Detail

Posture-dependent cranial outflow — the under-recognised pivot

In supine, most cerebral venous return exits via the internal jugular veins (IJVs). On standing, the IJVs behave as a Starling resistor above the thoracic inlet and outflow redistributes to the rigid, valveless vertebral–epidural and emissary plexuses. This preserves low dural sinus pressure and the trans-granulation gradient for arachnoid-granulation (AG) CSF absorption.

This preserves low dural sinus pressure and the trans-granulation gradient needed for arachnoid-granulation CSF absorption. In parallel, the CSF “canalicular” routes—perivascular (glymphatic) spaces and meningeal lymphatic channels—are more relied upon in the upright state, with respiratory/arterial pulsation and vertebral–cervical pumping routing solutes toward deep cervical nodes.

Trans-granulation pressure gradient: why venous pressure dictates CSF absorption

Townsend & Fargen 2021 described arachnoid villi/granulations behaving as pressure-gated conduits: bulk CSF absorption begins when subarachnoid space pressure (P_SAS) exceeds dural venous sinus pressure (P_SSS) by roughly 3–5 mmHg. As venous sinus pressure rises, P_SAS/ICP rises passively until this ΔP ≈ 3–5 mmHg is re-established—linking ICP tightly to sinus pressure (the classic Davson relationship).

In the upright state, keeping P_SSS low via vertebral/emissary outflow preserves that gradient and sustains AG-mediated clearance; conversely, any outflow bottleneck (e.g., jugular outlet narrowing at styloid–C1 or downstream venous thoracic outlet resistance) narrows ΔP, reduces CSF reabsorption, and predisposes to upright head-pressure.

In parallel, posture shifts a greater share of solute clearance to the brain’s canalicular routes: perivascular (glymphatic) exchange and meningeal lymphatics, with arterial/respiratory pulsation and vertebral–cervical pumping moving solutes toward the deep cervical nodes. Cadaveric work also delineates a CSF canalicular system running within the carotid sheath (in the adventitia of the IJV) to the subclavian vein; although in-vivo capacity remains to be quantified, upright reliance on these extra-venous pathways likely increases.

Figure 1: Summary of the positional changes in craniocervical venous structure between supine and upright posture

From Kosufi et al study 2020: “In the cervical region, the internal jugular vein (IJV) significantly collapses. In the craniocervical junction, the IJV shrinks in an upright posture; in contrast, the anterior condylar vein (ACV), anterior condylar confluence (ACC), and vertebral venous system—including the suboccipital cavernous sinus (SOCS), vertebral artery venous plexus (VAVP), and anterior internal vertebral venous plexus (AIVVP), as described in the figure—were enlarged in an upright posture. The following three venous routes become more prominent in the upright position: (1) the ACV, originating from the ACC and draining into the SOCS, VAVP, and AIVVP; (2) the LCV, originating from the ACC and draining into the SOCS, VAVP, and AIVVP; (3) the PCV, originating from the ACC or jugular bulb and draining into the SOCS, as represented by numbers in the figure. As opposed to those venous structures, the pterygoid plexus (PP), located anteriorly, does not undergo consistent changes depending on posture. In the intracranial space, the venous structure undergoes almost no change between postures. The vertebral venous plexus (VVP) at the cervical level, which could not be evaluated in this study, is shown as a dotted line.

Source: Kosugi, K., Yamada, Y., Yamada, M. et al. Posture-induced changes in the vessels of the head and neck: evaluation using conventional supine CT and upright CT. Sci Rep 10, 16623 (2020). https://doi.org/10.1038/s41598-020-73658-0

Pragmatically, this means vertebral and emissary plexuses must shoulder more flow upright; any bottleneck here will drop the AG gradient and impair CSF clearance.

In contrast to venous channels—which readily recruit emissary collateral veins—there is currently no convincing human evidence that adult meningeal lymphatic vessels form new collateral pathways in response to chronic egress bottlenecks. Human imaging outlines stereotyped routes to cervical lymph nodes; animal studies show that drainage falls with blockade or injury and is rescued by VEGF-C–driven lymphangiogenesis, implying limited spontaneous plasticity. Where alternate drainage is seen, it reflects use of existing pathways (e.g., olfactory/cranial nerve routes) rather than collateral neogenesis.

Beyond meningeal lymphatics, cadaveric work by Pessa 2023 delineates a CSF canalicular system: paired channels flanking the superior sagittal sinus that pass caudally within the carotid sheath in the adventitia of the internal jugular vein to terminate in the subclavian vein. Because CSF egress is gravity/posture-dependent, upright posture likely increases reliance on this extra-venous route.

Critically, the canalicular tract traverses the jugular outlet where the styloid/stylohyoid complex and the C1 transverse process form a narrow corridor, and then approaches the costoclavicular space before the subclavian vein—two well-described sites of outflow obstruction (styloidogenic IJV compression and venous thoracic outlet syndrome). Thus, even without assuming volumetric dominance over meningeal lymphatics, the positional anatomy of the canalicular system makes it intrinsically vulnerable at precisely the chokepoints we observe clinically; impaired patency at either level would raise downstream resistance to CSF clearance and plausibly manifest as upright head-pressure phenotypes.

Figure 2: Demonstration of the venous sagittal sinus and CSF channels   The sagittal sinus is a midline venous structure (between arrows) in the dura. CSF channels travel on either side of this venous sinus.

Figure 3: Cross-section diagram of CSF canalicular system, and anatomical route for CSF (yellow) to drain from the subarachnoid space directly into the subclavian vein.

Source: Figure 2 and 3: Pessa JE. Identification of a novel path for cerebrospinal fluid (CSF) drainage of the human brain. PLoS One. 2023 May 4;18(5):e0285269. doi: 10.1371/journal.pone.0285269. PMID: 37141309; PMCID: PMC10159342.

Clinical implication (why head pressure appears upright): if vertebral outflow is capacity-limited or lymphatic egress is sluggish or obstructed, the upright compensation fails—dural sinus and interstitial pressures creep up, and patients perceive upright head pressure (often with pulsatile tinnitus/crowding sensitivity).

1. Biomechanical and Glymphatic Collapse in Upright Posture

• In healthy individuals, upright posture triggers compensatory venous outflow redistribution and CSF reabsorption via arachnoid granulations and glymphatic clearance.

• In POTS/Long COVID/ME-CFS, CSF clearance is impaired due to glymphatic dysfunction (pericyte loss and astrocyte AQP4 mislocalisation).

• This worsens upon standing due to increased reliance on vertebral venous plexus, which may be narrowed or obstructed, seen on dynamic ultrasounds.

(Astrocytic aquaporin-4 polarity is essential for interstitial fluid clearance. Loss of AQP4 anchoring on astrocytic end-feet—due to inflammation or RAGE activation—causes perivascular oedema and intracranial stagnation.)

Diagram 4:The Glymphatic System

Source: Mogensen FL, Delle C, Nedergaard M. The Glymphatic System (En)during Inflammation. Int J Mol Sci. 2021 Jul 13;22(14):7491. doi: 10.3390/ijms22147491. PMID: 34299111; PMCID: PMC8305763.

Diagram 5: CSF Circulation, CSF outflow systems, and anatomy of CSF Compartments

Source: Shen MD. Cerebrospinal fluid and the early brain development of autism. J Neurodev Disord. 2018 Dec 13;10(1):39. doi: 10.1186/s11689-018-9256-7. PMID: 30541429; PMCID: PMC6292033.

2. Pericyte-Astrocyte–Endothelial Dysfunction

• Pericyte detachment under inflammatory/hypoxic stress leads to capillary leakiness, BBB disruption, and glymphatic stagnation.

• Astrocytes, instead of supporting flow and vasodilation, become reactive ("A1" phenotype), promoting local inflammatory cascades via IL-6, STAT3, and NF-κB.

(Telmisartan and other PPAR-γ activators partially restore pericyte coverage and reduce astrocytic IL-6/STAT3 reactivity.)

Diagram 6: The Neurovascular Unit showing the Pericytes lining blood vessels and the close relationship with the Astrocytes

Source: Sato, Y.; Falcone-Juengert, J.; Tominaga, T.; Su, H.; Liu, J. Remodeling of the Neurovascular Unit Following Cerebral Ischemia and Hemorrhage. Cells 2022, 11, 2823. https://doi.org/10.3390/cells11182823

3. Venous Outflow Impairment and Postural Hydrostatic Gradient

• Standing posture reduces CSF clearance by reversing the hydrostatic pressure gradient in cerebral venous drainage.

• Especially in internal jugular vein stenosis, reflux into cortical bridging veins and transverse sinuses contributes to elevated cortical venous pressure and interstitial brain oedema.

• Complicated by vertebral vein obstruction.   This combination seen frequently in upper cervical spine dysfunction aggravated by poor neck posture, with IJVs obstructed at C1 region, and base of neck, associated with Venous Thoracic Outlet Syndrome.

• This may mimic or evolve into a “functional intracranial hypertension” without raised opening pressure on lumbar puncture.

  
  

4. RAGE–TLR4–STAT3 Activation Sustains Barrier Dysfunction

• Chronic activation of the RAGE axis (via S100B, AGEs, HMGB1, etc.) maintains perivascular inflammation, pericyte loss, and interstitial trapping of metabolic waste.

• The glymphatic stasis is worsened by ECM stiffening, microglial activation, and aquaporin dysfunction.

(This explains the link between standing, neuroinflammation, mast cell activation, and worsening of “head pressure” in heat or stress.)

5. Neck, Fascia, and Thoracic Pressure

• Compressive structures (e.g., venous thoracic outlet, jugular stenosis, vertebral rotation, breast weight, fascia changes) may obstruct craniospinal venous flow.

• CSF Canalicular System operates when erect, and is potentially vulnerable at C1 and base of neck.   Potentially this moves more CSF/lymphatic fluid than the other lymphatic systems in the head and neck. 

• These create hydraulic bottlenecks, leading to paradoxical increased CSF pressure despite low or normal ICP on lumbar puncture.

(Many patients show temporary improvement with gentle manual lymphatic therapy, or positional changes that improve CSF clearance.)

Clinical Implications

• Standing head pressure may be a hallmark symptom of glymphatic and venous dysfunction, not psychogenic or migraine-based.

• Normal ICP on lumbar puncture does not exclude glymphatic failure or upright congestion. 

• Head pressure can be present when lying as well.  This may reflect increased venous pressure in the valveless vertebral system from Nutcracker, May-Thurner and Pelvic Congestion Syndromes.   These can also cause increased pain when seated, relieved when active

• MRI and lumbar puncture can be normal because the problem is upright congestion and glymphatic failure, not always raised pressure at rest.  MRIs usually require venography.   Accurate MRIs take time to be performed, and obstruction may be cleared by the time the scan is complete, so the “plug in the drain” effect of the cerebellar tonsils blocking the foramen magnum cannot be seen.   Pituitary compression (empty or partially sella) is common and not recognized as pathological, nor are the hyperintensities which are usually attributed to migraine or small vessel disease but in reality usually paravascular flow disruption.  High level retinal photography and OCTs can usually resolve the diagnosis and also show tortuosity reflecting pressure in the retinal vessels, that usually respond to telmisartan which aids in reducing the hypoxia

• Static imaging- MRI, ultrasound, echocardiography, venography etc are all limited by being usually done supine, and frequently miss posture-dependent dysfunction.   The evolution of dynamic ultrasonography, especially in the cervical vertebral, IJVs and other compression syndromes, as well as echocardiography has altered the “playing field,” as research using these is clearly demonstrating the underlying pathology.

• Collateral veins may enlarge… but there is no convincing evidence that adult meningeal lymphatic vessels form new collateral pathways in response to chronic egress bottlenecks.

• Patients are often mislabelled with “migraine,” “tension headache,” or “anxiety

• The sleep connection- symptoms often ease after sleep because glymphatic clearance is most active during deep sleep.   Poor sleep worsens symptoms → vicious cycle.   Protecting sleep is part of therapy, not laziness.

• Strong overlap between Long COVID, hypermobility syndromes, POTS and ME/CFS

• POTS driven by hypoxia, primarily in the brainstem dysregulating the autonomic nervous system and baroreceptor (pressure receptor) causing tachycardia and  shortness of breath when standing, and compounded by other vascular compression syndromes especially Thoracic Outlet Syndrome, Nutcracker, May-Thurner, Median Arcuate Ligament (MALS), Superior Mesenteric Artery and Pelvic Congestion Syndromes.   It is easily diagnosed using a NASA Lean test.  Evolving research has found the shortness of breath to be from preload failure, where the left ventricle function drops dramatically from lying to standing, caused by the baroreceptor/autonomic dysregulation tracked back to the brainstem hypoxia, compounded by direct affects in the cardiac and coeliac plexuses and influences from sympathetic activation from the thoracic and upper lumbar spine, and probably from the sympathetic nerves along obstructed lymphatics themselves. 

• Glucose dysregulation is also affected by the pressure change and hypoxia in the brainstem.   We believe the HPA axis is also affected potentially affecting hormone, adrenal (cortisol) function and unexplained weight gain.

  
  

What Helps

1. Positions:

• Recline at 120° or lie flat when needed.

• Elevate feet slightly for drainage.

• Avoid long periods sitting or standing still.   In some, seated is worse than standing, which may be traced back to pelvic congestion, nutcracker and similar syndromes affecting normal blood flow in the abdomen, pelvis and valveless vertebral system

2. Therapies:

• Gentle medical lymphatic drainage massage.  Avoid aggressive and untrained therapists

• Craniosacral therapy (from certified therapists)

• Breathing exercises, vagus nerve stimulation may assist.

• Fascial release and posture work.

3.Environment & Lifestyle

• Stay cool → fans, cooling vest, avoid hot showers/saunas.

• Control air quality → HEPA filters, reduce mould/chemical exposure.

• Pace activities → break tasks into chunks, plan rest lying flat.

• Eat smaller meals → avoids blood pooling in the gut.

• Neck posture → avoid long flexion (phone/laptop slouch).

• Stress care → calming activities reduce “fight or flight” overdrive.

• Backpacks/handbags too heavy with unbalanced weight distribution

4.Targeted support (with medical guidance)

• Anti-inflammatory/nervous system support (e.g., carnosine, NAC, omega-3s).

• Salt, electrolytes, fluids, compression garments if tolerated, professionally measured

• Lymphatic taping

• Ensure iron stores, Vitamin C and other vitamin levels are normal

• Nicotinamide riboside with magnesium supplementation to improve the functioning of the critical enzyme pyruvate dehydrogenase (PDH) in the energy cycle (as this enzyme is affected by hypoxia and viruses especially COVID

5.Research level: It is important to note these are at present investigational, and conservative management should be the primary treatment.   Surgical intervention should be considered only after treatment failure.

• Research is showing responses to “off-label” medication to reduce the hypoxia and improve the tissues and extracellular matrix where the end-products of the hypoxia accumulate, causing the accompanying metabolic dysregulation, fatigue and post-exertional malaise (PEM)

• Telmisartan to reduce impact of hypoxia on tissues, especially if significant retinal artery tortuosity

• Tirzepatide for metabolic and extracellular matrix (ECM) reprogramming- research suggests high level evidence in associated endometriosis and probably Long COVID.  It appears to improve the actual fascia and extra-cellular matrix.  Limited by cost and indications for use, and best at a low-dosage only

• Targeted metabolic solutions based on DNA and consideration for other research therapies such as peptides

• PEM is recoverable- with major components from diet, lifestyle, lymphatics and targeted metabolic management

Summary

Upright head pressure reflects real anatomical and physiological congestion in the brain.

• It arises from a failure to clear CSF and interstitial waste due to vascular, glial, and fascial changes.

• Proper posture, gentle therapies, and targeted treatment of the glymphatic–venous–inflammatory axis are essential to address the cause—not just the symptoms.

• Collaterals are common, especially at the back of the neck, the emissary veins often large, but lymphatic collaterals do not appear to be forming.

• It is not psychological and does not always show up on a lumbar puncture

• Managing posture, environment, and inflammation can ease symptoms and improve brain fluid flow