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  • Writer's pictureGraham Exelby

A 50 Year Journey in Medicine

Dr Graham Exelby November 2023


As I finish 50 years in medicine (45 years in general practice), experience has taught me that we never stop learning. The need to keep asking “why” and not just accepting “what is the accepted” has taken me in a direction where I see health as a combination of what we inherit (our genes), what we do with our lifestyles, and what life’s circumstances inflict on us.


Learning to treat problems like atopic eczema and irritable bowel syndrome (IBS) with diet was a significant factor in this direction change, courtesy of Dr Merv Garrett, an allergist and pioneer in Australia. Then as I journeyed down the rabbithole that is POTS and Fibromyalgia things started to come together.


COVID-19 then answered many of the questions that kept popping up- how a virus (and here add trauma, mould, parasites, sustained stress) can activate threat receptors (Toll-like receptors, or TLRs) which then activate Mast Cells that are responsible for the cytokine storm that is what happens in COVID.


Simplified, Covid activates the TLRs (primarily TLR4) which then activate mast cells which produce inflammatory cytokines, especially Interleukins 6 (IL-6) and 8 (IL-8) and Tissue Necrosis Factor alpha (TNFa) which cause damage in tissues including microglial cells, and this process is responsible for the characteristic Small Fibre Neuropathy (SFN) and from this the autonomic instability of dysautonomia, POTS and Long-COVID.


The level of inflammation is so severe in COVID that microemboli are often formed and from this we get inflammatory and microembolic damage. Sometimes amyloid is also found in the fibrin clots, which leads in the future to the same linking into Alzheimers and Parkinson’s Diseases.


At the same time TLR2 activation is associated with impaired function in another glial cell, the astrocytes, so there is an astrocyte/glutamate dysfunction that has been seen in conditions such as autism, and visual snow. This affects the function of the vital glymphatic system (the brain's sewer).


The addition of DNA assessments from Dr Valerio Vittone revealed common threads of DNA mutations in these syndromes, and a way to tackle these disabling conditions. DNA mutations in mast cells, the COMT, methylation, oxidative stress and other mutations have opened the door to successful treatments, ignoring the normal advice given in Long Covid to “accept your lot.”


I have combining research from many areas over the years, and this is continuing as I continue to pursue the craniovascular and glymphatic changes in the brain, as well as tackling areas where genetic factors are critical such as:

  • Homocysteine and APO E4 (the importance of these forgotten measures have been highlighted in Covid management)

  • COMT mutations which have relevance in POTS, Fibromyalgia, and many others.

  • Aortic root and arch dilatation

Major influences on my work:

  • Firstly the pioneering work of Dr Merv Garrett in diet,

  • Lawrence Afrin and his cohorts in the USA on mast cell activation syndrome

  • Griffith University research on brainstem connectivity, glymphatic function and TRP mutations that affect natural killer cell function and glymphatic function itself

  • Kjetil Larsen and others in Thoracic Outlet, Jugular Outlet Syndrome and the impact of neck pathology and posture on craniovascular perfusion

  • The regular assistance from Profs Pete Smith and Jon Jenkins when the "going gets tough" and I cannot see a clear direction, and more recently from Dr Kevin Lee (endocrinology and nuclear medicine) and Rebecca Ryan (gastroenterologist) to discuss the implications of our clinic findings.

  • A new team of physiotherapy researcher clinicians to discuss possible management protocols to deal with the mechanical and hydraulic problems we have been finding.

  • Radiologists Drs Vini Nascimenco, Zane Sherif and a number of sonographers to work out how to best image some of the clinical findings. In particular assessment of the newly-discovered extremely high correlation of POTS with stylohyoid compression of the Internal Jugular Vein/s at C1, found in 90% of the newer scanned patients.

  • Accurate retinal photography primarily through optometrist Alan Ming assessing retinal arterial, venous change and looking for pressure in the optic discs.

  • Most importantly with help from Dr Valerio Vittone, to understand the underlying DNA mutations that lie behind both POTS and Long Covid and most diseases.

The primary "drivers" in POTS essentially boil down to compression of the Internal Jugular Veins, the venous Thoracic Outlet Syndrome and upper cervical neck pathology, aggravated by hypermobility especially in patients with EDS. Most demonstrate varying degrees of intracranial hypertension and/or intracranial vascular pressure dysfunction. Glymphatic function is critical, as complicating vascular compression, both venous and arterial, we have found lymphatic obstruction especially in the head and neck, although it is impossible to radiologically prove this. This has engendered a radical change in management, the details of which are being worked out, with trials underway in lymphatic therapy along with structured exercise programs which is showing significant responses.



Techniques being employed:

  • Dynamic ultrasounds to assess major areas such as the Thoracic Outlet, Median Arcuate Ligament Syndrome, Nutcracker and May-Thurner Syndromes and relevance in particular in POTS (and resistant Long Covid). Standard angiography in a lying position does not see the changes seen in dynamic scanning

  • Retinal photography and Carotid Intimal Thickness Scanning, started in 2008 as tools to assess small and medium vessel disease, now expanded to assess vertebral artery flow

  • Heart rate variability studies in postural assessments of POTS, fibromyalgia as similar diseases

  • Holter monitoring calibrated for heart rate variability to assess patterns of autonomic instability

  • SPECT and other scanning to assess cerebral perfusion.

  • Continuing detailed history and alignment with likely genetic predisposition.


By taking a thorough history in all facets of a person’s life, with a family history, and using appropriate investigations, early identification means that potential problems may be halted and may be reversed.


As the current research progresses in Covid, there is glimpse into the near-future with better management of many diseases, including Alzheimers, Parkinson's, Multiple Sclerosis, cancer, auto-immune diseases, and even arthritis as the pathways are being unlocked. Time will tell as medicine moves into very exciting new areas.

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