A Neuroinflammatory Model for ME/CFS (a hypothesis)

Dr Angus Mackay talks with us about his theory that neuroinflammation is the cause of ME/CFS (and Long Covid related post-viral fatigue syndrome).
Presentation for MECFS Canterbury, 14th February 2024.
Angus hopes that as brain imaging techniques develop, the model will be used by researchers to explore and develop a better understanding of this debilitating disease.
The model revolves around a dysfunctional and inflamed hypothalamus, the master gland within the brain, and the stress-response centre within it, called the paraventricular nucleus (PVN), that responds to all significant stressors including viral and other shocks.
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ADDITIONAL RESOURCES:
✦ Timestamped slide list further below
✦ Pdf of the slide deck - drive.google.com/file/d/1Hxjj...
✦ Biography and Outline of presentation drive.google.com/file/d/1QNyO...
✦ The published papers on the theory:
- Mackay, A. (2021). A Paradigm for Post-Covid-19 Fatigue Syndrome Analogous to ME/CFS. Frontiers in neurology, 12, 701419-701419. doi.org/10.3389/fneur.2021.70...
- Mackay, A. (2019). A neuro-inflammatory model can explain the onset, symptoms and flare-ups of myalgic encephalomyelitis/chronic fatigue syndrome. Journal of primary health care, 11(4), 300-307. doi.org/10.1071/HC19041
- Mackay, A., & Tate, W. P. (2018). A compromised paraventricular nucleus within a dysfunctional hypothalamus: A novel neuroinflammatory paradigm for ME/CFS. International journal of immunopathology and pharmacology, 32, 205873841881234. doi.org/10.1177/2058738418812342
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CONTENT /SLIDE LIST:
00:00 Introduction
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02:54 An analogy of ME/CFS - the two jars
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05:31 Presentation topic: A Neuroinflammatory Model for ME/CFS
06:02 A Personal Journey - Gaining insight into ME/CFS
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08:46 Why has Neuroinflammatory Hypothesis for ME/CFS been slow to take off?
- Neuorinflammation in ME/CFS brains chronic but at a low-level
- Brain does not contain nociceptors (pain/ heat receptors)
- The red herrings
15:57 The Hypothalamus (master gland) is Key
18:55 Hypothalamic Paraventricular Nucleus (PVN) - Eureka!!
20:38 Possible Triggering Mechanism of ME/CFS
23:20 Glial-cells (brain /Central Nervous System immune cells)
27:01 Increasing Evidence of Neuroinflammation in ME/CFS
32:48 ME/CFS Symptoms (Explanation of)
36:04 PEM (Post-exertional malaise), Flares and Relapses
42:21 Stressors and Paraventricular Nucleus (PVN)
45:16 PVN is same target for Triggering Stressors and Perpetuating Stressors of ME/CFS
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45:49 A Neuroinflammatory Model for ME/CFS
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49:59 The Long COVID Conundrum
52:30 Possible triggering mechanism for Long-COVID related ME/CFS
53:39 Evidence of Neuroinflammation in Long-COVID
54:29 Further Evidence of Neuroinflammation in Long-COVID (ME/CFS)
55:30 A Neuroinflammatory Model for ME/CFS applicable to Long-COVID related ME/CFS
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55:56 Future Needs
1:00:53 Pacing How to Pace Yourself with ME/CFS (or Fibromyalgia or Long-COVID related ME/CFS)
- Avoid unnecessary stressors
- Listen to your body
- Manage your symptoms
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1:03:04 The Papers Related to this Model
- Mackay, A. (2021). A Paradigm for Post-Covid-19 Fatigue Syndrome Analogous to ME/CFS. Frontiers in neurology, 12, 701419-701419. doi.org/10.3389/fneur.2021.70...
- Mackay, A. (2019). A neuro-inflammatory model can explain the onset, symptoms and flare-ups of myalgic encephalomyelitis/chronic fatigue syndrome. Journal of primary health care, 11(4), 300-307. doi.org/10.1071/HC19041
- Mackay, A., & Tate, W. P. (2018). A compromised paraventricular nucleus within a dysfunctional hypothalamus: A novel neuroinflammatory paradigm for ME/CFS. International journal of immunopathology and pharmacology, 32, 205873841881234. doi.org/10.1177/2058738418812342
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1:03:44 Questions
1:03:59 Is it a genetic susceptibility or does this susceptibility change over time? As many people report coping with many stressors, and then something similar happens that then triggers ME/CFS.
1:06:40 Example shared of a recent relapse caused by exposure to more sunlight when blinds were removed for cleaning.
1:08:27 Angus’s connection dropped out
1:08:33 How did people find the talk?
1:10:10 Angus returns
1:10:30 Does this model resonate with people?
- Eye pain; feeling of a swollen head.
1:13:35 Thank you Angus
1:15:18 We need researchers to explore and validate the model now
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1:16:42 Thank you to the funders of MECFS Canterbury

[@elizabethsmith8599]

Awesome, your model fits so well with me too.

[@lyndawashbrook8018]

Thank you this was very helpful Dr MacKay. I am in Canada and on a waiting list for a specialist, by doing my own research have been able to realize that what I am going through is all part of Me/CFS , Fibromyalgia which I was diagnosed first. I actually felt the ME creeping in as the heaviness I first felt in my shoulders start to creep down my arms and legs. Now it's an effort to use my arms at times I am hoping it will be a slow process. I spent a day in Dunedin and enjoyed it very much especially Cadbury 's , I found a Rum and Raisin bar that I had not tasted since I left Ireland. Many Thanks.

[@JaneSullivan-yl8zc]

I found the model presented by Dr MacKay made a lot of sense to me. I was diagnosed with CFS in 2007. Like Dr MacKay I led a very active life, competing in triathlons and off road running events, plus working, being a Mum and organising community triathlon events. I had glandular fever in my last year at university. Before being diagnosed with CFS, I was presenting with what seemed like a chronic allergic reaction potentially from chemical exposure. Fast track to 2020 and I had a fall accident resulting in a dislocated fractured ankle. After slow recovery and meeting the Budapest criteria I was diagnosed with Complex Regional Pain Syndrome (CRPS). I have often asked medical specialists over the past 3yrs, "Do you think having a CFS diagnosis made me a sitting duck for CRPS"? Quite possible would be the reply. Some of the theories regarding CRPS are similar to CFS - neuroimmune in origin and involvement of glial cells. LDN is a treatment being trialled for CRPS. So a lot of similarities - maybe I was predisposed to developing these conditions. I wish you well with future research and would be happy to participate in any future studies.