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Functional characterization of muscle fibres from patients with CFS

Dolphin

Senior Member
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Again, because of my lack of knowledge of muscles, I probably won't be able to contribute much to this thread. But like with their other research, it seems very interesting.

Functional characterization of muscle fibres from patients with chronic fatigue syndrome: case-control study.

Int J Immunopathol Pharmacol. 2009 Apr-Jun;22(2):427-36.

Pietrangelo T, Toniolo L, Paoli A, Fulle S, Puglielli C, Fan G, Reggiani C.


Source

Dept. Basic and Applied Medical Sciences (BAMS), Center for Excellence on Ageing (CeSI), University - G. dAnnunzio- Chieti-Pescara, Chieti, Italy. tiziana@unich.it


Abstract

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities.

Although immunological and psychological aspects are present, symptoms related to skeletal muscles, such as muscle soreness, fatigability and increased lactate accumulation, are prominent in CFS patients.

In this case-control study, the phenotype of the same biopsy samples was analyzed by determining

i) fibre-type proportion using myosin isoforms as fibre type molecular marker and gel electrophoresis as a tool to separate and quantify myosin isoforms,

and

ii) contractile properties of manually dissected, chemically made permeable and calcium-activated single muscle fibres.

The results showed that fibre-type proportion was significantly altered in CSF samples, which showed a shift from the slow- to the fast-twitch phenotype.

Cross sectional area, force, maximum shortening velocity and calcium sensitivity were not significantly changed in single muscle fibres from CSF samples.

Thus, the contractile properties of muscle fibres were preserved but their proportion was changed, with an increase in the more fatigue-prone, energetically expensive fast fibre type.

Taken together, these results support the view that muscle tissue is directly involved in the pathogenesis of CSF and it might contribute to the early onset of fatigue typical of the skeletal muscles of CFS patients.
 

mellster

Marco
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Wowsa! I think I hypothesized about a possible shift from slow to fast-twitching fibres in one of my early posts cause that matches my experience after exercise and might explain increased muscle-twitching (via increased number of fast-twitching fibres). This might also explain why there is no decrease in strength, but a much faster exhaustion/depletion.
 

Marco

Grrrrrrr!
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This is a good run of papers Dolphin. Good find.

This chimes very much with my own experience also as I still appear to cope with heavy loading but not with any aerobic activity. Slow twitch fibres are also the type that we use when standing still - something many of us can't tolerate for long.

As is often the case - bodybuilding types have a good handle on muscle physiology :

Functionally, slow-twitch fibers are used for aerobic activities requiring low-level force production, such as walking and maintaining posture. Most activities of daily living use slow-twitch fibers.

http://www.musclemagfitness.com/bod...twitch-muscle-fibers...what-it-all-means.html


I would hope of course that they have controlled for the possiblity that the change to type II muscle fibres isn't just as a consequence of an enforced sedentary lifestyle (again my own experience would suggest this is not the case).


More interesting, to me, is that factors such as a high fat diet leading to obesity, or ageing result in reduced mitochondrial efficiency and a switch to type II (glycolytic myofibres) muscle fibres :

MAP kinase phosphatase-1 - a new player at the nexus between sarcopenia and metabolic disease


More recently we have been able to provide mechanistic insight in to the pathway linking MKP-1 to mitochondrial function. We have found that MKP-1 is a key regulator of the master controller of mitochondrial biogenesis, PGC-1? [15]. When mice are fed a high-fat diet, the expression levels of MKP-1 in skeletal muscle increase which results in a reduction in PGC-1? levels. In contrast, PGC-1? levels are maintained in mice lacking MKP-1 [15]. Consistent with the notion that PGC-1? promotes oxidative myofiber composition MKP-1-deficient mice are refractory to the switch from oxidative to glycolytic myofibers seen in wild type mice fed a high fat diet and remain lean.

http://www.impactaging.com/papers/v2/n3/full/100135.html

This suggests to me that a major part of our problem is either a primary or secondary mitochondrial dysfunction.
 
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I would hope of course that they have controlled for the possiblity that the change to type II muscle fibres isn't just as a consequence of an enforced sedentary lifestyle (again my own experience would suggest this is not the case).

This is a real problem and not easily addressed because 'sedentary' can mean different things (for exmple it may exlude non aerobic exercise such as yoga which can maintain muscle tone ), while different bodies can respond differently over differing periods of time, and as noted diet may impact upon the type of response (likely mediated by genetic variability) to sedentary behaviour. I think to have effective controls for M.E/CFS physiology research, there needs to be not only age and gender matching but a much more detailed set of controls including BMI, duration of lifestyle habit and lifetime diet, plus age based comparison. Finding muscle changes in long term ill 40 year olds is one thing - finding it in teenagers with less than a years ill health, may be something vey different.

IVI
 
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This is a real problem and not easily addressed because 'sedentary' can mean different things (for exmple it may exlude non aerobic exercise such as yoga which can maintain muscle tone ), while different bodies can respond differently over differing periods of time, and as noted diet may impact upon the type of response (likely mediated by genetic variability) to sedentary behaviour.

It seems unlikely sedentary behavior is causing these muscle abnormalities, since those abnormalities can cause the initial symptoms of M.E. In this case of chicken versus egg, it's pretty obvious to most PWME that the symptoms came first, followed by a forced reduction in activity levels.

On a more personal level, I think the deconditioning theories regarding M.E. are pretty worthless. I started having a (thus far) significant recovery 10 days ago, immediately after starting neurotransmitter-regulating supplements. My ability to do physical stuff, like climb a flight of stairs, immediately increased dramatically. I've had sore muscles the past few days from being more active, but I think it would be impossible for a PWME to confuse M.E. muscle pain with this normal soreness, after months or years of enduring the M.E. pain. Undoubtedly there is muscle deconditioning, but it is a very minor concern: it is not even close to being the limiting factor when it comes to physical activity.
 

Dolphin

Senior Member
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17,567
As somebody who became ill as a sporty/athletic teenager, I'm not convinced muscle symptoms are due to deconditioning - as I never went to bed. Nobody in our house used to go to bed (my father has always been self-employed so that may have influenced him) - the most I did was potter around at home for a couple of days (I wasn't diagnosed till five years into it). I had over 100 physiotherapy (=physical therapy) appointments in the early years when I was constantly on my feet in full time education and had all sorts of weird muscle symptoms. It certainly felt like there was something odd in my muscles. I could accept there might be some central factors but I'm not at all convinced deconditioning could explain the symptoms as I never was that deconditioned.
 

Sean

Senior Member
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7,378
Similar story here, Dolphin.

Conventional deconditioning just does not fit my particular circumstances preceding, during, and for at least 4 years after onset. You do not have to be very active to avoid serious deconditioning, and I easily met that mark. Yet I continued seriously deteriorating, no matter what I did.

Far as I can see, the overall evidence fairly strongly points to towards any deconditioning being a secondary consequence of the limited activity imposed by ME/CFS, not a cause of it.
 

Dolphin

Senior Member
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17,567
Authors deal with whether finding could be down to disuse

I actually hadn't read this one.

The discussion section is very interesting.

Here, they briefly explain why they don't think the changes are down to disuse:

The absence of a change in CFS fibre size deserves some comment. First, although it is at odds with the hypothesis that disuse might contribute to the slow-to-fast shift discussed above, it is in agreement with previous histological studies on CSF patient muscles that were unable to find any significant evidence for muscle atrophy (3, 10).

Our idea is that the increased presence of fast fibre in CFS muscle do not depend on muscle disuse but may have an unknown molecular origin that needs to be deeply investigated.

This reported lack of muscle fibre atrophy finds support in the results of the expression profile studies (Pietrangelo et al, 2009 IJIPP in press). In fact, all CFS muscle samples showed down- regulation of the transcripts for forkhead box 03A (FOXO3A), H1 histone family member X (H1FX), ubiquitination factor E4A (UBB4A), proteasome (prosorne, macropain) 26S subunit non-ATPase 3 (PSMD3), and proteasome (prosome, macropain) subunit beta type 2 (PSMB2). Collectively, the down-regulation of these genes suggests that the catabolic and atrophic processes that could reduce muscle mass are less active.

3. Lane RJ, Barrett MC, Woodrow D, Moss J, Fletcher R, Archard LC. Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):362-7.

10. Edwards RH, Gibson H, Clague JE, Helliwell T. Muscle histopathology and physiology in chronic fatigue syndrome. Ciba Found Symp. 1993;173:102-17; discussion 117-31.

"Pietrangelo et al, 2009 IJIPP in press"= Pietrangelo T, Mancinelli R, Toniolo L, Montanari G, Vecchiet J, Fan G, Fulle S. Transcription profile analysis of vastus lateralis muscle from patients with chronic fatigue syndrome. Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):795-807.
 

Marco

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I think we can safely rule out deconditioning as a cause for ME. There never was any evidence for the proposition and quite a lot of evidence to counter it. As for deconditioning as a perpetuating factor, again there is no evidence of any affect specific to ME. This doesn't exclude the possibility that if deconditioning has occurred in a subset of patients that this could skew the results of physiological studies such as this.

The new International criteria (if eventually widely adopted or at least used in tandem) do not require 6 month duration for a diagnosis and therefore raise the possibility of studying patients before there is any realistic chance of deconditioning (post onset).

Unfortunately I can't find the full Pietrangelo et al paper but the reference to Lane et al is interesting.

From the abstract :

Inactivity would be expected to result in a shift to type 2 fibre predominance and fibre atrophy, but type 1 predominance (23%) was more common than type 2 predominance (3%), and fibre atrophy was found in only 10.4% of cases.

Muscle histometry in patients with chronic fatigue syndrome generally did not show the changes expected as a result of inactivity. However, patients with abnormal lactate responses to exercise had a significantly lower proportion of mitochondria rich type 1 muscle fibres.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169994/

Edited to add :

From reading the Lane et al abstract and the slightly contradictory results I suspected we were dealing with an 'Oxford' cohort. This is indeed the case. The full Lane et al paper is very well worth reading though as general background and in particular the comments about type II dominance in those suffering heatstroke (a tendency in mitochondrial diseases).
 

mellster

Marco
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Agreed - I do not experience any atrophy/weakness related symptoms though I have muscle-twitching and suffer from PENE occasionally. I even don't experience a high degree of soreness, I def think this is not related to deconditioning. Also there are theories that muscle-twitching is a result of immune-system activity rather than something wrong at the location of the nerves/muscles themselves, more like a sort of hyper-excitability.
 
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I just did a tiny bit of reading on slow vs fast twitch muscles, and it's pretty interesting. I'm wondering if it's type IIx found more in the study, which doesn't have as much mitochondria and myglobin (and capillaries?), versus IIa which has similar amounts to slow twitch muscles. If so, maybe a process in our bodies (faulty mitochondria, insufficient oxygen) causes the body to switch to type IIx.

Also an interesting note in wikipedia regarding type IIx fast twitch muscles:
It can contract more quickly and with a greater amount of force than oxidative muscle, but can sustain only short, anaerobic bursts of activity before muscle contraction becomes painful (often incorrectly attributed to a build-up of lactic acid).

I know that not-quite-lactic-acid burning sensation very well :p
 

Dolphin

Senior Member
Messages
17,567
I just did a tiny bit of reading on slow vs fast twitch muscles, and it's pretty interesting. I'm wondering if it's type IIx found more in the study, which doesn't have as much mitochondria and myglobin (and capillaries?), versus IIa which has similar amounts to slow twitch muscles. If so, maybe a process in our bodies (faulty mitochondria, insufficient oxygen) causes the body to switch to type IIx.

Also an interesting note in wikipedia regarding type IIx fast twitch muscles:


I know that not-quite-lactic-acid burning sensation very well :p
Yes, it is 2x that are different and 2a that are the same.

I can't imagine it is a pre-existing condition (I played a lot of sports competitively) so the body must switch.
 

mellster

Marco
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Yes, I even continued kickboxing when I weakened but had not significant PENE at that time at I noticed the increased twitching, first only following strenuous exercise, then it became permanent slowly over time (but 90% of the twitches occur at night and/or at rest). Def a body switch.
 

mellster

Marco
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One thing that's odd though is that the twitches are everywhere, like although mostly in extremities and butt, some are in tongue or scalp, so it seems weird that those areas are affected too as you would not think that those areas suffer a lot of oxidative stress or endure hard workouts - which points again to a widespread body switch which might be "mis"-induced by ME/CFS type conditions (or their causing pathogens).
 

anciendaze

Senior Member
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1,841
I have regularly had people surprised at my short-term muscle strength, despite being seriously debilitated in terms of aerobic capacity and orthostatic tolerance. In one case I was able to lift a chest single-handedly and carry it downstairs, while another person my size was looking for help. This is very different from having stamina. An explanation in terms of fast vs slow muscle fibers makes sense, but does not reach the original cause.

I think it is obvious this is not the result of some peculiar strength training, but I will state this here to avoid confusion: I have not been doing resistance training. The only form of exercise which has helped, beyond very low-level things like walking to the mailbox regularly, has been slow stretching, as described here. The primary aim in that book is to avoid injuries during subsequent exercise. My experience is that ME/CFS patients are especially vulnerable to these, even in ordinary activity -- for reasons that have never been explained. I even do some stretches before I try to get out of bed. Waiting until a patient shows up at an exercise class, when they may have already pushed close to their limits, indicates a complete misunderstanding of the problem.

This is very different from general deconditioning.

For our Latin interlocutor, "Sed nescio quo modo nihil tam absurde dici potest quod non dicatur ab aliquo philosophorum."
 
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Marco

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As for deconditioning as a perpetuating factor, again there is no evidence of any affect specific to ME.

I did of course mean 'effect' but the original would also be true "again there is no evidence of any affect specific to ME"
 

Marco

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Strangely enough, I was lining up to do a comparison between the autonomic symptoms of diabetic/cardiac autonomic neuropathy and autonomic symptoms in ME/CFS (as you do and there's a large overlap) when this thread popped up.

One paper on diabetic autonomic neuropathy contains this :

Recognizing and treating diabetic autonomic neuropathy

"Limited exercise tolerance is due to impaired sympathetic and parasympathetic responses that normally augment cardiac output and redirect peripheral blood flow to skeletal muscles".

http://www.ccjm.org/content/68/11/928.full.pdf

That being the case you would expect impaired blood flow to peripheral muscles to also result in impaired oxygen delivery (relative to demand) which would be expected to impact more on the aerobic slow twitch fibres. I can't say how reduced blood flow would impact on the fast twitch glycolytic fibres. Its plausible that over time this impairment might result in a compensatory relative switch from slow to fast twitch fibres.

Turns out there does appear to be a switch to fast twitch muscle fibres in Type II diabetes which

Altered fiber distribution and fiber-specific glycolytic and oxidative enzyme activity in skeletal muscle of patients with type 2 diabetes.

CONCLUSIONS:

Reduced oxidative enzyme activity in muscle of type 2 diabetic patients is most likely due to a reduction in slow oxidative fibers. Increased glycolytic and oxidative enzyme activities in individual muscle fibers are closely related to measures of long-term glycemic control and whole-body insulin sensitivity and could therefore represent a compensatory mechanism of the muscle in function of the altered glucose metabolism.

http://www.ncbi.nlm.nih.gov/pubmed/16567834
 

Murph

:)
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