Fascial-Lymphatic Obstruction and Brainstem Hypoxia in Long COVID and POTS

Dr Graham Exelby June 2025- a Preliminary paper

Abstract: Emerging clinical observations suggest that post-exertional malaise (PEM) in Long COVID and POTS is not solely the result of cellular energy failure but may be driven by toxic metabolite accumulation in the extracellular matrix (ECM), compounded by lymphatic and glymphatic clearance failure. Fascial decompression and targeted lymphatic therapy have been shown to resolve head pressure and PEM in real-time, implicating the ECM as a dynamic reservoir of hypoxia-induced inflammatory mediators. This paper integrates anatomical, metabolic, and immunological findings to propose a unifying mechanism linking impaired interstitial drainage, brainstem hypoperfusion, and neuroimmune sensitization.

1. Introduction: Post-exertional malaise is a defining feature of ME/CFS, Long COVID, and POTS, characterized by a disproportionate symptom flare following minimal exertion. Traditional models emphasize mitochondrial dysfunction and impaired energy metabolism. However, novel lymphatic therapies now suggest that PEM can be reversed by mechanical fascial decompression, pointing to the ECM and lymphatic system as active pathophysiological players.

2. Clinical Observation: A lymphatic therapist using Vodder manual therapy reports that in patients with PEM and head pressure, opening the cervical, axillary, and parasternal lymphatics in supine position, followed by seated decompression at T8, results in:

• Immediate reduction in interscapular and suprascapular oedema

• Resolution of head pressure

• Significant reduction in PEM symptoms

This effect is reproducible and appears to correlate with mechanical unlocking of fascial and lymphatic structures that interface with thoracic duct drainage, spinal accessory nodes, and cranial venous return.

3. Molecular Hypothesis: ECM Toxicity and Glymphatic Failure Hypoxia in Long COVID and POTS (due to impaired vertebrobasilar flow, IJV obstruction, TOS, or MALS) leads to accumulation of:

• Lactate, succinate

• HMGB1, S100A8/9

• Glutamate, ATP, purines

• AGEs

These molecules are pro-inflammatory and neurotoxic, activating RAGE, TLR4, P2X7, and mast cell receptors in the ECM. Without lymphatic or glymphatic clearance, they persist in perivascular and interfascial spaces, driving:

• Neuroinflammation

• Head pressure

• Sympathetic overdrive

• PEM

  
  

4. Anatomical-Mechanical Convergence Points:

• T8 rotation: May reflect subconscious compensation for splanchnic venous congestion (MALS), tightening thoracic duct and impairing drainage

• C1 fascial release: Myodural bridge tension may impair 4th ventricular CSF flow; decompression restores vagal tone and CSF pulsatility

• Low-lying cerebellar tonsils: Dynamic crowding at foramen magnum obstructs venous outflow; elevation relieves pressure

5. Therapeutic Implications:

• Manual lymphatic drainage using Vodder therapy, especially targeting thoracic and cervical convergence zones, can rapidly reverse ECM-mediated congestion

• Fascial techniques addressing T8 rotation and C1 dural tension may restore brainstem glymphatic and vagal outflow

• These interventions should be paired with antioxidant therapy (e.g., NAC, ALA), mast cell stabilizers, and positional therapy (45° supine)

• A regenerative peptide currently being investigated, may support vascular integrity and lymphatic endothelial repair, enhancing the clearance of ECM-borne metabolites and reducing microvascular permeability.

• Telmisartan functions dually as an angiotensin receptor blocker and PPARγ agonist, modulating RAGE expression, reducing oxidative stress, and indirectly dampening HIF-1α activation. Its use may promote glymphatic perfusion, stabilize endothelial function, and shift the immune-metabolic profile toward resolution.

6. Conclusion: This clinical breakthrough reframes PEM not solely as an intracellular energy crisis, but as a failure of ECM detoxification. It positions the fascial-lymphatic interface and glymphatic function at the core of recovery strategies for Long COVID, POTS, and CFS. Future studies should prioritize imaging of ECM dynamics, molecular profiling of interstitial fluids, and validation of therapeutic decompression techniques.