Lymphatic Obstruction in POTS, CFS, and Long COVID: A Call for Integrated Therapeutic Approaches

- Unblocking the Invisible Network: Fascia, Mast Cells, and the Clinical Relevance of Lymphatic Obstruction in Complex Syndromes

Dr Graham Exelby, Michelle Hill (Vodder Therapist), Deborah Calleja (Osteopath-Perrin Therapist) May 2025

Abstract

Postural Orthostatic Tachycardia Syndrome (POTS), Chronic Fatigue Syndrome (CFS), and Long COVID are multisystem disorders marked by autonomic instability, immune dysregulation, and neuroinflammatory symptoms like fatigue and brain fog.  Lymphatic obstruction, an underrecognized driver, impairs extracellular matrix (ECM) detoxification, glymphatic clearance, and autonomic regulation.

Clinical research reveals that chronic inflammation via RAGE–TLR4–NF-κB–CCL2 signalling and mast cell–mediated collagen degradation stiffens the interstitial terrain, while amino acid imbalances (lysine, ethanolamine) disrupt gut-lymphatic flow, potentially contributing to non-alcoholic fatty liver disease (NAFLD) and small intestinal bacterial overgrowth (SIBO).

Mechanical bottlenecks, particularly at the cranio-cervical junction and base of neck, exacerbate these effects. This paper proposes an integrated model using Vodder Manual Lymphatic Drainage (MLD), Perrin Technique, mast cell stabilization, and fascial/postural physical therapy to restore lymphatic flow and address mechanical vulnerabilities like thoracic outlet syndrome (TOS) and Ehlers-Danlos Syndrome (EDS). By reframing lymphatic dysfunction as a central, modifiable mechanism, clinicians can improve outcomes in these refractory syndromes.

Introduction

Lymphatic dysfunction is a frequently overlooked yet physiologically central contributor to chronic disorders such as POTS, CFS, and Long COVID. These conditions share features of neuroimmune dysregulation, orthostatic intolerance, and extracellular matrix (ECM) toxicity—symptoms often driven or sustained by compromised lymphatic clearance.

The lymphatic system plays a vital role in clearing cytokines, toxins, and macromolecular waste from both the ECM and glymphatic pathways. When drainage becomes impaired—whether by structural compression, fascial tension, or inflammatory oedema—interstitial stagnation ensues. This perpetuates immune activation, tissue rigidity, and autonomic imbalance.

Recent discoveries have deepened our understanding of this network. Studies by Boisserand (1)  and Albayram (2) confirm direct anatomical and regulatory links between lymphatic vessels, sympathetic ganglia, and cervical lymphatic output. These findings suggest that impaired flow at critical junctions—particularly at the base of the neck—may directly influence brainstem perfusion, sympathetic tone, and intracranial pressure.

At the molecular level, activation of RAGE and TLR4 receptors by damage-associated molecular patterns (DAMPs) initiates NF-κB signalling and upregulation of CCL2, promoting mast cell recruitment and ECM degradation. This creates a feedback loop of interstitial rigidity, neuroinflammation, and lymphatic collapse. Mast cell mediators such as histamine, prostaglandins, and MMPs further destabilize collagen and compromise vessel integrity.

Compounding this, COVID-19–associated hypoxia and metabolic dysfunction have been shown to impair lysine and ethanolamine metabolism—both essential for maintaining collagen stability and phospholipid membranes. These amino acid disruptions weaken the gut-blood barrier and impair chylomicron transport, potentially leading to NAFLD and SIBO through gut lymphatic stasis.

Current medical approaches focus on symptomatic suppression but neglect the immune-metabolic-fascial terrain sustaining these syndromes. This paper advocates a paradigm shift: targeting lymphatic obstruction as a modifiable driver of chronic dysautonomia. We propose integrating Vodder MLD, Perrin drainage sequencing, mast cell stabilization, and fascial/postural therapy into routine clinical care, particularly in patients with mechanical vulnerabilities such as TOS, EDS, and cervical trauma.

Why This Matters Clinically:

1.     Lymphatic Flow Is Not Passive: The lymphatic system actively interfaces with the immune system, ECM, autonomic nerves, and cerebral drainage. Obstruction at the IJV, thoracic duct, back of neck, or T8 can have cascading effects.

2.     Fascia as a Dynamic Regulator: Fascia envelops and mechanically regulates lymphatics. Inflammation, dehydration, or fibrosis halts interfacial glide, collapsing lymphatic initiation and perpetuating immune dysregulation.

3.     Extracellular Matrix (ECM) Dysfunction: Often overlooked, the ECM acts as both a mechanical scaffold and biochemical signalling platform. In chronic illness, it becomes a reservoir for cytokines, toxins, and inflammatory debris. ECM fibrosis or stagnation increases interstitial pressure, impairs nutrient and signal exchange, and compresses initial lymphatic vessels—blocking the very first step in lymphatic uptake. Proper lymphatic drainage depends on ECM pliability and low interstitial resistance. MLD and fascia-directed therapies help rehydrate, decompress, and 'reset' the ECM, facilitating lymphatic engagement.

4.     Mast Cell Dysregulation: Mast cell mediators (histamine, cytokines, prostaglandins) stiffen fascia, reduce lymph flow, and degrade ECM architecture. Controlling mast cells is thus a prerequisite to restoring drainage.

5.     Mechanical Obstruction Syndromes: Structural compressions like TOS, Nutcracker, or scoliosis are not just vascular—they impair lymphatic return, sympathetic outflow, and vagal signalling.

6.     Cervical Lymphatic Bottleneck at the Base of the Neck: The convergence of the thoracic duct and right lymphatic duct into the subclavian veins at the base of the neck forms the final common outflow tract for nearly all lymphatic drainage in the body. Obstruction or mechanical tension at this junction—due to fascial compression, cervical rib anomalies, sternocleidomastoid hypertrophy, thoracic inlet restriction, or venous congestion (e.g., IJV compression)—results in systemic lymphatic stasis. This can elevate intracranial pressure, impair glymphatic drainage, and provoke downstream effects in the liver, gut, and extremities. MLD targeted at the cervicothoracic transition can relieve this choke point, re-enable interstitial clearance, and improve systemic symptom burden.

Lymphatic Obstruction and Autonomic connection

Lymphatic obstruction is often seen clinically, sometimes even extending across the anterior chest wall when the thoracic outlet compression is marked.   It is almost to impossible confirm radiologically, although large nodes may be seen eg in the cervical collar.  The anatomy of the arteries and veins in the head and neck is such that the lymphatics envelop the vessels, so any physical compression of the vascular structure must result in varying degrees of lymphatic obstruction.   

These lymphatic vessels have no valves, so sustained obstruction will cause backpressure into the Glymphatic system with the risk of Idiopathic Intracranial Hypertension.   Venous compression can produce a similar problem.  

Boisserand et al.2019 (1) confirmed in mice studies that “vertebral lymph vessels connect to peripheral sensory and sympathetic ganglia and form similar vertebral circuits connecting to lymph nodes and the thoracic duct.   They showed that the connection between lymph vessels and sympathetic ganglia occurred at the surface of the ganglia revealing a hitherto unknown anatomical interaction between the autonomous nervous system and vertebral lymphatic vessels.   They are closely apposed around the chains of sensory and sympathetic nervous ganglia, so lymphatic vessels may provide molecular signals to the sympathetic neurons that control vascular tone of lymphatic ducts and cerebral arteries and arterioles.”

“Previous observations by the authors also showed that adrenergic fibres connect to the thoracic lymphatic duct and also innervate the wall of lymph node arterioles.   The crosstalk between spine LVs and the sympathetic system is thus likely relevant for the regulation of peripheral lymph and glymphatic drainage and may coordinate them with the activity of brain and spine tissues. The authors speculate that a regulatory loop may link meningeal lymph vessels, sympathetic chain neurons and both CNS and peripheral fluid drainage.”(1)

Albayram et al.2022 (2) showed “dural lymphatic structures along the dural venous sinuses in dorsal regions and along cranial nerves in the ventral regions in the human brain and they detected direct connections between lymphatic fluid channels along the cranial nerves and vascular structures and the cervical lymph nodes.  They also identified age-related cervical lymph node atrophy and thickening of lymphatics channels in both dorsal and ventral regions, findings which reflect the reduced lymphatic output of the aged brain.”(2) 

“Macromolecules, waste products, and excess fluid from most tissues are known to drain into the systemic lymphatic system.   Classically, absorption of CSF occurred through arachnoid granulations and villi of the intracranial and spinal venous sinuses.   More recent animal studies have demonstrated CSF-ISF drainage via meningeal lymphatic vessels and along the cranial nerves into deep cervical lymph nodes.”  According to their study result, the vascular-carotid space in the neck is very important for the CSF-ISF drainage from the brain.”(2) 

The discovery of this inter-relationship between vertebral lymph vessels and sympathetic ganglia provides a tantalizing possibility to help explain reduced flow in the middle cerebral artery and brainstem – from the increased head pressure at the jugular foramen and the increased venous pressure at the crowded craniocervical junction as the posture changes from lying to standing, the venous return changes from Internal Jugular to Vertebral venous plexus.   If the IJV is obstructed, for example by poor head-forward posture, the venous pressure in the vertebral system is increased further, and the lymphatics too are increasingly compressed, and theoretically the activation of the sympathetics in the lymphatic walls.   

Previous observations by Jacob et al (1) showed that “adrenergic fibres connect to the thoracic lymphatic duct and also innervate the wall of lymph node arterioles.   The crosstalk between spine lymphatic vessels and the sympathetic system is thus likely relevant for the regulation of peripheral lymph and glymphatic drainage and may coordinate them with the activity of brain and spine tissues. The authors speculate that a regulatory loop may link meningeal lymph vessels, sympathetic chain neurons and both CNS and peripheral fluid drainage.”(1)

Clinic studies confirmed vertebral venous obstruction at the base of the neck, often with retrograde flow.   While the lymphatic obstruction cannot as yet be confirmed radiologically, it simply cannot be affected when the emissary veins are grossly dilated and vertebral in retrograde flow.

Yousry et al.2023 (3) investigated post-lumbar puncture postural headaches finding dilatation of the anterior internal vertebral venous plexus in 85% of their symptomatic subjects.    It becomes an issue if both areas are compromised, just as in POTS where multiple compression areas are found (including the Nutcracker, Median Arcuate Ligament and May-Thurner Syndromes.)   

Linking the head and neck to the intra-abdominal compression areas is the Azygous System, where increasingly it also appears there may be anatomical variations or even obstruction, but difficulties in imaging make this impossible to prove at the present time.  Abnormal connection of the hepatic and suprarenal segments of the IVC results in azygous or hemiazygous continuation, which may be isolated or associated with other anomalies.(4)

The Role of Lymphatic Obstruction in POTS, CFS, and Long COVID

The lymphatic system is integral to ECM homeostasis, immune surveillance, and glymphatic clearance. In POTS, CFS, and Long COVID, lymphatic dysfunction manifests as:

• ECM Stagnation: The ECM becomes a reservoir for cytokines, environmental toxins (e.g., mould biotoxins, heavy metals), and pathogens, driving chronic inflammation and mast cell activation.

• Glymphatic Impairment: Reduced clearance of neurotoxic waste via meningeal lymphatics and perivenous pathways contributes to brain fog, headaches, and cognitive dysfunction.   This is vital it Long COVID where the glymphatic system is often rendered dysfunctional.

• Autonomic Dysregulation: Lymphatic stasis at key sites (e.g., thoracic duct, cervical lymphatics) disrupts vagal tone and sympathetic balance, exacerbating orthostatic intolerance and fatigue.

Anatomical contributors to lymphatic obstruction include:

• Thoracic Outlet Syndrome (TOS): Compression of the thoracic duct and subclavian vein impairs lymphatic return, contributing to oedema and neurovascular symptoms.

• EDS with Low-Lying Cerebellar Tonsils: Hypermobility and tonsillar ectopia increase dural tension, impairing cerebrospinal fluid (CSF) outflow and glymphatic drainage.   When standing, the cerebellum drops down into the foramen magnum potentially obstructing vertebral venous and lymphatic flow from the brain.   Vertebral venous studies have confirmed obstruction and often retrograde flow.

• Upper cervical trauma: Head forward posture, cervical hinging and rotational movements may impact on both vascular and lymphatic flow.   Malrotation of C2/3 may also affect the IJV flow in the carotid sheath, as demonstrated in Spectral CT venography.

• IJV Compression: Seen in conditions like Eagle Syndrome, IJV occlusion reduces venous and lymphatic outflow, exacerbating intracranial pressure and neuroinflammation.  IJV obstruction is also seen from dysfunctional IJV valves (using dynamic ultrasonography) and at the venous angles associated with a venous Thoracic Outlet Syndrome.

Figure 1: Lymphatic System

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/b/b0/2201_Anatomy_of_the_Lymphatic_System.jpg

Figure 2. Lymph Chains Head and Neck

Source: drzero. Cervical Adenopathy and Neck Masses. 2019 Radiology Key. https://radiologykey.com/cervical-adenopathy-and-neck-masses/

Figure 3. Lymph Nodes of Posterior of Neck

Source:  Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See &quot;Book&quot; section below)Bartleby.com: Gray&#039;s Anatomy, Plate 603, Public Domain, https://commons.wikimedia.org/w/index.php?curid=566548

Figure 4. Schematic model of the brain lymphatic system and its drainage pathways. The green signal at the orifices of neural foramina represents lymphatic fluid

Source: Albayram, M.S., Smith, G., Tufan, F. et al. Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes.

Figure 4. The Azygous System

Source: OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons. https://upload.wikimedia.org/wikipedia/commons/2/28/2132_Thoracic_Abdominal_Veins.jpg

Post-Exertional Malaise as an Indicator of ECM and Glymphatic StasisPost-exertional malaise (PEM)—a hallmark of CFS and Long COVID—may reflect transient accumulation of metabolic byproducts, cytokines, and redox-reactive intermediates in the extracellular matrix (ECM) and glymphatic channels. Recent clinical observations demonstrate that targeted Vodder MLD, especially when applied through fascial layers at T8 and the deep cervical chains, can reverse PEM within minutes.

This suggests that the substrates of PEM are not purely intracellular or systemic but reside in the interstitial and perivascular compartments. The immediate reduction in interscapular oedema and head pressure in upright posture further implicates T8-mediated hydraulic stagnation as a convergence point for venous, lymphatic, and autonomic dysfunction. MLD appears to restore drainage of hypoxic metabolites and inflammatory mediators, supporting a dynamic, reversible model of PEM grounded in ECM saturation and glymphatic failure.

Gut-Lymphatic-Metabolic Dysfunction in COVID-19

Emerging evidence suggests that COVID-19 and associated hypoxia disrupt gut-lymphatic and metabolic pathways, amplifying lymphatic obstruction and systemic inflammation in Long COVID, POTS, and CFS. These mechanisms include:

• Amino Acid Dysfunction: COVID-19 may impair metabolism of lysine and ethanolamine, essential amino acids involved in protein synthesis, lipid metabolism, and cellular signalling. Lysine is critical for collagen and connective tissue integrity, while ethanolamine is a precursor for phosphatidylethanolamine, a key component of cell membranes and lipoproteins like chylomicrons. Dysfunctional metabolism may weaken the gut-blood barrier and impair lymphatic vessel integrity, contributing to ECM stagnation and inflammation. While direct evidence linking lysine/ethanolamine dysfunction to Long COVID is limited, these pathways warrant further investigation given their role in connective tissue and lipid transport.

• RAGE–TLR4–NF-κB–CCL2 Axis and Mast Cell–Collagen Crosstalk: Environmental triggers (e.g., mould, stress, viral infection, hypoxia) activate the Receptor for Advanced Glycation End Products (RAGE) and Toll-like Receptor 4 (TLR4), converging on NF-κB signalling to drive transcription of inflammatory mediators such as IL-6 and CCL2 (MCP-1). CCL2 promotes mast cell recruitment and microglial activation, perpetuating inflammation and ECM degradation. Mast cell mediators (histamine, tryptase, MMPs) further fragment collagen, stiffen fascia, and disrupt lymphatic compliance. These loops impair immune surveillance, cerebral drainage, and vascular tone—core features in POTS, CFS, and Long COVID.

• Gut-Blood Barrier Disruption: Severe SARS-CoV-2 infection compromises the gut-blood barrier, increasing intestinal permeability and allowing microbial translocation (e.g., lipopolysaccharides) into the bloodstream. This triggers systemic inflammation and immune dysregulation, common in Long COVID and CFS. Gut barrier dysfunction also impairs mesenteric lymphatic function, reducing clearance of inflammatory mediators and toxins.

• Gut Lymphatic and Chylomicron Pathway Impairment: The mesenteric lymphatics coordinate gut-brain communication, immune priming, and hepatic detoxification. In COVID-19, lymphatic stasis may disrupt chylomicron transport, which carries dietary lipids from the gut to the liver via the thoracic duct. Impaired chylomicron pathways could contribute to lipid accumulation in the liver, a hallmark of NAFLD. Lymphatic dysfunction also creates a stagnant gut environment, fostering SIBO—a condition increasingly diagnosed in Long COVID and CFS patients presenting with bloating, diarrhoea, and dysbiosis.

• Contributions to NAFLD and SIBO: NAFLD, characterized by hepatic fat accumulation, may be exacerbated by impaired chylomicron transport and gut lymphatic stasis, which disrupt lipid metabolism and increase hepatic toxin exposure. SIBO, driven by lymphatic congestion and dysmotility, perpetuates gut dysbiosis and endotoxemia, further taxing the liver and lymphatic system. These conditions amplify systemic inflammation, contributing to fatigue, brain fog, and autonomic dysfunction in POTS, CFS, and Long COVID.

Figure 5: Lacteal- villi of small intestine showing blood vessels and lymphatic vessels

Henry Vandyke Carter, Public domain, via Wikimedia Commons. https://upload.wikimedia.org/wikipedia/commons/c/c1/Gray1061.png

Therapeutic Interventions

Neurochemical Shifts with Manual Lymphatic Drainage: Historic Insights with Contemporary Implications

A pivotal yet under-recognized study from 1978 by Kurz et al (5) demonstrated that manual lymphatic drainage massage in patients with chronic lymphedema elicited significant shifts in neurohormonal excretion, suggesting central autonomic and inflammatory modulation. In 29 patients, urinary excretion of adrenaline increased by 50%, noradrenaline by 19%, and 5-HIAA (a serotonin metabolite) by 21%. Conversely, serotonin decreased by 22%, and histamine excretion rose dramatically by 129%. These findings—absent in control patients—suggest that MLD exerts a neurohumoral effect via sympathetic activation (adrenergic output), modulation of serotonergic tone, and likely mast cell degranulation as evidenced by histamine flux. Notably, other metabolic parameters such as creatinine, thyroxine, and mineral excretion remained unchanged, reinforcing that MLD selectively modulates the neuroimmune axis rather than inducing nonspecific metabolic shifts.

In the context of Long COVID, POTS, and CFS, these neurochemical findings underscore the relevance of MLD in rebalancing autonomic tone, flushing inflammatory mediators like histamine and serotonin from interstitial compartments, and potentially downregulating central sensitization pathways. Given the mast cell–collagen–lymphatic triad identified in these syndromes, MLD may both mobilize interstitial fluid and recalibrate neuroinflammatory signalling.

Importantly, the study authors proposed combining MLD with antihistaminergic and antiserotonergic agents—a suggestion now echoed in clinical protocols integrating H1/H2 blockers and mast cell stabilizers in POTS and Long COVID. These early findings lend empirical support to MLD as a neuroimmune intervention, not merely a mechanical drainage technique, and warrant renewed clinical and mechanistic investigation.

Vodder Manual Lymphatic Drainage (MLD)

Manual Lymphatic Drainage (MLD), particularly the sophisticated and autonomically informed Vodder technique, represents a pivotal intervention in managing POTS, CFS, MCAS, and related syndromes characterized by lymphatic stagnation, vascular compression, and extracellular matrix (ECM) dysfunction.  Unlike conventional fluid mobilization methods, Vodder MLD works at the intersection of anatomical drainage, fascial mobility, neuroimmune signalling, and detoxification physiology. It achieves this through rhythmical, non-invasive manual techniques that stimulate lymphangion contractility, reduce sympathetic overdrive, and restore interstitial terrain coherence.

At the core of this process is the ground substance of the ECM—a dynamic, gel-like colloidal matrix composed primarily of glycosaminoglycans (e.g., hyaluronic acid), proteoglycans, and structural glycoproteins. This matrix is not merely a scaffold; it is the biochemical and mechanical milieu through which cells exchange nutrients, hormones, immune signals, and metabolic waste. It also plays a key role in tissue hydration, pH buffering, and the binding of cations and growth factors.

However, the ground substance has limited buffering capacity and quickly becomes a toxic reservoir in the presence of chronic inflammation, infection, or stagnation. As cytokines, histamines, reactive oxygen species, and environmental toxins accumulate, the colloidal consistency thickens, leading to impaired diffusion and cellular signalling.

This is particularly problematic in patients with connective tissue disorders, vascular compression syndromes, or autonomic dysregulation, where ECM congestion contributes to mast cell instability, brain fog, and impaired vagal tone.

In this context, MLD helps "liquify" the ground substance by mechanically deforming the matrix and mobilizing bound toxins toward lymphatic uptake. This effect is achieved via gentle shearing of fascial layers, which reactivates anchoring filaments that open initial lymphatic capillaries. These vessels are embedded in the superficial and deep fascia and serve as the gateway for clearing the lymph obligatory load—that portion of interstitial fluid that cannot be reabsorbed by venous capillaries and must be returned to circulation via the lymphatics.

The lymph obligatory load consists of high-molecular-weight proteins, cell debris, immune cells, and fat-soluble waste products—elements that cannot re-enter the bloodstream directly due to their size or charge. In chronic illness, the accumulation of this load overwhelms lymphatic capacity, resulting in oedema, tissue hypoxia, and immune dysregulation. MLD significantly reduces this burden by enhancing lymphatic uptake, increasing lymphangion contractility, and rerouting flow through collateral pathways when central drainage is impaired (e.g., thoracic duct obstruction or IJV compression) (Foldi & Foldi, 2006 (6)).

Crucially, MLD also supports craniospinal clearance.   Intraoral and craniocervical MLD techniques decompress the pterygoid plexus, palatine lymph ring, and dural lymphatic outflow, improving drainage from the orbit, brainstem, and cerebellum. This is especially relevant in patients with intracranial hypertension, fourth ventricle crowding, or dural tension at C0/C1 and T8, where glymphatic stagnation contributes to symptoms like tinnitus, occipital headaches, dizziness, and neuroinflammation.

By improving glymphatic and CSF mobility through the meningeal lymphatics, MLD can relieve cognitive fog, visual strain, and vagal flare-ups characteristic of POTS.

The autonomic effects of MLD are equally profound. Gentle stimulation of cutaneous lymphatic territories downregulates sympathetic activity while enhancing vagal tone, increasing heart rate variability (HRV) and stabilizing autonomic inputs to the heart and gut. Lymphatic support to the mesentery and liver also improves bile flow, digestive motility, and clearance of fat-soluble toxins—reducing the burden on the gut-brain axis and supporting microbial balance.

Summary of Vodder:

By addressing the terrain-level dysfunction at the heart of these complex syndromes, Vodder MLD offers a uniquely integrated solution: it restores fluid dynamics across the ECM–lymph–nervous system triad, facilitates neuroimmune communication, and reduces the chronic congestion that underlies many “invisible” illnesses. Its precision and systemic reach make it a cornerstone of integrative care in long COVID, CFS, and dysautonomia.

Vodder MLD uses precise, rhythmic techniques to stimulate lymphangion contractility, enhance interstitial fluid clearance, and modulate autonomic tone. Its benefits include:

• ECM and Gut Detoxification: MLD clears inflammatory metabolites, toxins, and microbial byproducts from the ECM and mesenteric lymphatics, reducing mast cell triggers and gut-related inflammation.

• Enhanced Glymphatic Clearance: Craniocervical and spinal MLD restores CSF mobility and glymphatic outflow, alleviating brain fog and pressure-related symptoms.

• Autonomic Reset: Light-touch techniques promote parasympathetic dominance, improving heart rate variability and reducing POTS symptoms.

• Gut-Lymphatic Support: MLD to the mesentery, ileocaecal valve, and liver enhances motility, bile flow, and chylomicron transport, potentially mitigating NAFLD and SIBO risk.

Perrin Technique

The Perrin Technique is a manual therapy approach developed by osteopath Dr. Raymond Perrin. It is designed to assist with lymphatic drainage and autonomic regulation.   This therapy aims to stimulate the flow of lymph and cerebrospinal fluid (CSF) by using gentle manual techniques along the spine, head, chest with a specific sequence.

It is particularly effective in CFS and Long COVID, where it, alongside other osteopathic techniques:

• Relieves fascial tension at the T8 region and craniocervical junction, improving thoracic duct and glymphatic drainage.

• Enhances diaphragmatic movement, supporting lymphatic flow and chylomicron transport.

• Reduces neuroinflammation by facilitating glymphatic waste clearance.

Mast Cell Stabilization

Mast cell activation syndrome (MCAS) is prevalent in these conditions, driven by ECM toxin accumulation, gut dysbiosis, and lymphatic stasis. Strategies include:

• Pharmacologic Agents: Low-dose antihistamines (e.g., cetirizine, famotidine) and mast cell stabilizers (e.g., cromolyn sodium).

• Lymphatic Support: MLD reduces ECM and gut-derived triggers like cytokines and lipopolysaccharides, stabilizing mast cells.

• Nutritional Support: Quercetin, vitamin C, and omega-3 fatty acids modulate inflammatory signalling.

Physical Therapy for Fascial and Postural Correction

Fascial dysfunction and poor posture exacerbate lymphatic obstruction, particularly in EDS and TOS. Interventions include:

• Fascial Release: Myofascial release restores interfacial glide, reopens collapsed lymphatic channels, and supports gut lymphatic flow.

• Postural Correction: In EDS with low-lying cerebellar tonsils, exercises to improve cervical lordosis and reduce forward head posture alleviate dural tension and enhance CSF outflow.

• TOS Management: Stretching and strengthening of the scalene, pectoralis minor, and trapezius muscles decompress the thoracic outlet, improving lymphatic and venous return.

• Cervical Stabilization: In IJV compression, gentle neck strengthening and alignment exercises reduce pressure on the jugular vein and associated lymphatics.

Clinical Considerations

Clinicians must adopt an integrated approach to address lymphatic and gut-lymphatic dysfunction:

• Assessment: Evaluate for signs of lymphatic stasis (e.g., oedema, tissue stiffness), fascial restriction, gut dysbiosis (e.g., bloating, diarrhea), and postural abnormalities. Imaging (e.g., MRI for cerebellar tonsils, Spectral CT and dynamic doppler for IJV flow) and gut health markers (e.g., SIBO breath testing) may guide diagnosis.

• Individualization: Tailor MLD and physical therapy to the patient’s connective tissue laxity, autonomic sensitivity, and gut health status.

• Collaboration: Coordinate care among Vodder-certified therapists, Perrin practitioners, physical therapists, and physicians to address multifactorial contributors.

Conclusion

Lymphatic obstruction, compounded by gut-lymphatic and metabolic dysfunction, is a critical driver of POTS, CFS, and Long COVID. COVID-19-related amino acid dysfunction, gut-blood barrier impairment, and disrupted chylomicron pathways may further exacerbate lymphatic stasis, contributing to NAFLD and SIBO. Vodder MLD, Perrin Technique, mast cell stabilization, and targeted physical therapy offer powerful tools to restore lymphatic flow, improve fascial mobility, and address gut-related inflammation.

By integrating these approaches, clinicians can tackle the interstitial, neurolymphatic, and gut-lymphatic terrain, offering hope to patients refractory to conventional treatments. Further research is needed to confirm the role of lysine and ethanolamine dysfunction and their impact on gut-lymphatic pathways.

Clinical findings that PEM can resolve through lymphatic decompression challenge the notion that this symptom reflects irreversible mitochondrial damage. Instead, PEM may reflect reversible hydraulic and immunometabolic stagnation within the ECM and glymphatic systems. By clearing inflammatory and hypoxic byproducts from these compartments, therapies like Vodder MLD reframe PEM not as a fixed metabolic bottleneck but as a dynamic failure of clearance—one amenable to interventional treatment.

References

1.     Jacob, L., Boisserand, L.S.B., Geraldo, L.H.M. et al. Anatomy and function of the vertebral column lymphatic network in mice. Nat Commun 10, 4594 (2019). https://doi.org/10.1038/s41467-019-12568-w

2.     Albayram MS, Smith G, Tufan F, Tuna IS, Bostancıklıoğlu M, Zile M, Albayram O. Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes. Nat Commun. 2022 Jan 11;13(1):203. doi: 10.1038/s41467-021-27887-0. PMID: 35017525; PMCID: PMC8752739.

3.     Yousry,I et al. Cervical MR Imaging in Postural Headache: MR Signs and Pathophysiological Implications. AJNR. 2023. https://www.ajnr.org/content/22/7/1239/F4

4.     Congenital Thoracic Venous Anomalies. Radiology Key   https://radiologykey.com/congenital-thoracic-venous-anomalies/

5.     Kurz W, Wittlinger G, Litmanovitch YI, et al. Effect of Manual Lymph Drainage Massage on Urinary Excretion of Neurohormones and Minerals in Chronic Lymphedema. Angiology. 1978;29(10):764-772. doi:10.1177/000331977802901007

6.     Foldi, M., & Foldi, E. (2006).  Földi's textbook of lymphology for physicians and lymphedema therapists 2nd ed. Elsevier, Urban & Fischer Verlag, München, Germany, ©2006Wittlinger, A., Wittlinger, M., Wittlinger, H. & Wittlinger, D. (2018). Dr. Vodder's Manual Lymph Drainage a practical guide, 2nd ed. Thieme.