Christopher Snell 2012 Lecture – "Clinical exercise testing in CFS/ME research and treatment"

Christopher Snell 2012 Lecture – "Clinical exercise testing in CFS/ME research and treatment"


After mentioning the lecture in the last post, I'm giving this very excellent lecture of his an post of its own.

I think the lecture is very helpful and ties in nicely with the work done by Kathleen and Alan Light (see Alan Light's 2007 and 2011 lecture).

If I had some more energy, I would write down some take home message – but alas, this has to suffice for now.

Update:
This came in via Tom Kindlon and Jan van Roijen.

Alan Light 2011 Lecture: Gene Expression Biomarkers for Chronic Fatigue & Fibromyalgia Syndromes

As a follow-up to the last post, here is his 2011 lecture (about 1 hour) by Alan Light for OFFER Utah about his very excellent ME/CFS gene-expression study.

This is objective data that there is biological reason for the symptoms [in ME/CFS and Fibromyalgia].

You may want to switch to 1080p HD to best view the slides.
(Part 1 Part 2 Part 3 Part 4 Part 5)

My take-home messages:

1. 70% of ME/CFS patients have Fibromyalgia (FMS) symptoms. And Fibromyalgia gets worse after exercise, even if the definition for FMS does not specify for it. And a majority of FMS patients (but not all) have ME/CFS symptoms.

2. TRPV1 contributes to the body's temperature set point.

3. Alan Light found a sensory definition of fatigue (The nerves at the muscle tell the brain "You are tired") in ME/CFS that contributes to the desire to use the muscles less. It is related to "actual" muscle fatigue ("The muscle is about to fail"), but it is not the same.

4. In both ME/CFS and FMS there is a 40% subgroup, that has a Ad2A (vasoconstriction) decrease. That gene is responsible for preventing orthostatic intolerance (OI / POTS). 70% patients with this gene expression profile have orthostatic intolerance, and 20% without have POTS (it might depend when and how you measure POTS).

5. FMS without CFS patients look like controls after execercise, but have different baseline levels. P2X4, TRPV1 and IL10 are expressed higher at baseline.

6. Gene expression as biomarker for ME/CFS and Fibromyalgia? Specificity 94% (6% of false negatives) and sensitivity of 65% (35% of false positives), good but not excellent biomarker, could be improved. Might be clinically available within 2 to 3 years.

7. The orthostatic subgroup should be treated differently.

8. Pregabalin or Gabapentin decrease the level of pain and of mental fatigue - maybe.

9. The cause could be increase of sensitivity of fatigue and pain, or dysfunction of the sympathetic nervous system.
(My comment, this the only flaw of Alan Light's work I can think of. He is leaving out one possibility: Of course it could be that there is an actual increase of fatigue and pain due to a pathologically increased muscle exhaustion in ME/CFS and FMS patients. If the nerves are sensing something, it could actually be there – doh!)

10. This is objective data that there is biological reason for the symptoms.
(Translated to English: "The psychosomatic school can go and f*ck themselves.")

As an addendum:
Don't miss Christopher Snell's 2012 lecture, which ties in nicely!

Alan Light 2007 Lecture: The Physiology of Chronic Pain and Fatigue

OFFER Utah (warning, their website plays music...) has a lot of lectures regarding ME/CFS on their OFFER Utah Youtube Channel. They have some very good and interesting lectures (and some less so). If you haven't already, you should subscribe to their Youtube channel, add the feed to your RSS-Reader, etc. ...

One very interesting video is this 44 minutes lecture by Alan Light:

"The Physiology of Chronic Pain and Fatigue" Dr. Alan R. Light.

This presentation by Alan R Light was made during the 2007 OFFER Provider's Conference. This lecture shows basically where Alan Light came from and his studies that lead up to the ME/CFS post-exertional gene-expression study "the Lights" (he and his wife Kathleen Light) have done together with Lucinda Bateman.

I had these take home messages:

1. Acute pain and fatigue sensing are protective and evolutionary important to prevent depletion or injury of important systems. If an living being has an impairment in sensing of pain and fatigue, it will usually die quite quickly. So there are multiple pathways in a living being to measure this information.

2. There are many concepts of fatigue. For ME/CFS fatigue is not sleepiness, fatigue is not failure of the muscle, but a sensory event – one could move the muscle with enough willpower.

3. The sensing of muscle-pain and fatigue happens by nerve sensory-endings located between the muscle and the blood vessels. Several metabolites (Lactate, ATP, pH/protons) are measured together by receptors (e.g. P2X4, P2X5, ASIC3, TRPV1) working together.

4. Fatigue and pain share receptors, but are not the same.

5. The sympathetic nervous system can restrict blood vessels to muscles that are not fatigued and increase blood flow to muscles that are.

6. Mononuclear blood cells have these receptors too, as they need to go "where the action is", where damage is, where things are going wrong and they are circulating through the muscles that are used.

7. Enhanced muscle pain is caused by cytokines, and if the blood flow is not increased (if the sympathetic nervous system does not regulate it properly), the metabolites in the muscles build up, and with it fatigue and pain.

8. The NIH (and the medical profession at general) are not interested and it is very difficult to get funding for these studies. All his research depends on the support by the university of Utah. There is some old medical "knowlegde" ("these receptors don't function at physiological ranges" etc.) that needs to be challenged and updated. This research that should have been done 25 years ago and the NIH is dragging its feet.
(I find it ironic that it is Alan Light's research in ME/CFS that improves the understanding in biological and medical sciences of how pain and fatigue work – after all the damage that Strauss et. al. have done with their psychosomatic bullshit, after all the damage Wessely and Sharpe are still doing today)

Don't miss Alan Light's 2011 follow-up lecture!

And don't miss Christopher Snell's 2012 lecture, which ties in nicely!

David Bell Lecture: 25 Year Follow-up in Chronic Fatigue Syndrome

David Bell has given a very interesting lecture (albeit a bit longish, but very rewarding to watch) on how his patients do after 25 years, and the Massachusetts CFIDS/ME & FM Association has done an excellent job of publishing it on their web-page:

Here is a short summary (about 1 page), and long summary (about 10 pages). You can view the video of the lecture (55 minutes) and the video of the Q&A session (42 minutes) – both links open a video in flash-format in a new window. MassCFIDS has made a fine presentation of the lecture with a side-by-side video of the speaker, an index and the slides.

I had two take-home-messages:

1. After the "acute" phase of ME/CFS, which can last several month to years, patients fall in one of three categories.

Dr. Bell felt that the single most useful criterion in gauging overall well-being was how many hours someone spent engaged in upright activity each day: "hours of actually doing something, like work, school, or cleaning; not just sitting around, vegging-out watching TV." Some people with CFIDS/ME log only one to five hours of cumulative activity a day, he said (those hours generally aren't consecutive; people might be active for only a few minutes at a time). Healthy people, or controls, averaged 15 hours of daily activity; the remitting patients, about 13, fairly close to the level of "normals." 

With the exception of those who had recovered, however, no one seemed totally okay this time around. Forty percent (40%) had essentially no symptoms and apparently normal activity, but they were not as well as controls. Among the 20% who remained disabled, many experienced increasing debility over time. The remaining 40% (the remitters) still had symptoms, but their activity level was close to normal; that sounds like a good outcome, but in fact many ultimately experienced a return of symptoms or an erosion in activity level.

So, after the acute phase:

• 20% never get well, most of them are bedbound
• 40% get well (albeit not completely), stay that way and have left the disease almost behind
• 40% improve after the acute phase, but never get "really well" and very slowly deteriorate over the years

And the "gradual-onset" patients might be patients that had an asymptomatic "acute" phase:

Also on the topic of XMRV, Dr. Bell suggested the possibility that many people may have been exposed to this virus without developing symptoms. … He said he wouldn't be surprised if it turned out that some people who were fine at age 20 became symptomatic as they aged, perhaps developing CFIDS/ME at age 40 or later. This is another subject for future research.

2. About half of the ME/CFS patients either have arranged themselves ("I'm fine, I don't have problems." despite being still seriously restricted), or they don't talk with their doctors about their symptoms ("I don't mention my problems, no way!").

"Health-identity confusion" seemed to plague those in the remitting category. They considered themselves to be in good health, but all still had symptoms and abnormal lab tests indicating that something was physically amiss. On the symptom scales, the remitting patients' scores fell about half-way between those of controls and those of chronic patients. A healthy person's score on one symptom might be zero (0), e.g., a chronic/persistent person's score might be 10; and a remitter's, in the middle at five.  

Bell remarked, that many patients will say, "I'm opting out of this system." … "When I called them, I asked, 'Have you told your current doctor that you have this illness?'  A lot of them said something like, 'I'm not going to subject myself to that!"