The experience of fatigue in neurological patients with Multiple Sclerosis: a thematic synthesis, 2020, Newton et al

Paywall, https://www.physiotherapyjournal.com/article/S0031-9406(16)30489-8/pdf
Sci hub, https://sci-hub.tw/10.1016/j.physio.2016.11.004

 

Note, the first author is Georgina Newton (not to be confused with Julia Newton) along with colleagues at the School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham.

I disagree on (c) and (d). The problem is the wrong instruments have been used for (c) (supramaximal twitch interpolation is not a useful measure of fatigue and is often misinterpreted by neurologists who don't understand exercise physiology or metabolic biochemistry and do not understand the relationships between peripheral and 'central' fatigue) and on the contrary to (d), those questionnaires are highly sensitive and it is a lack of effective treatments that is the primary problem.

Their qualitative synthesis suffers from a garbage-in-garbage-out type problem, namely low-quality/suggestive-quality research treated as useful/conclusive research and lack of appreciation of study-subject bias, namely only popular cultural themes were examined by researchers in the first place.

 

May I ask you, if wouldn´t be too complicate, could you elaborate?

I ask this because I am pretty interested in this issue. I don´t see a logical point to be able to successfully differentiate between these two, so it remains that it must be an empirical difference.

I guess supramaximal twitch analysis indicates peripheral causes to indeed feel fatiqued, but is negative here. So you say, that this is false negative. Instead an fatique might occure because of the difficult movements of the patients? Or maybe because they may often move quite seldom?

I see some point here. MS is known to be CNS driven, so a if there would appear any effect on the periphery there could be a feed back loop. I admit that I am not convinced.

 

I might have time to explain in more detail later, but for now:

We cannot conclude either way, due to flawed testing/modelling.
It is important to point out three aspects: (a) people feel fatigue at far lower levels of exertion and only rarely exert maximally hence the body never relies on a reduction in maximal exertion as a measure of fatigue (b) most studies using the supramaximal twitch methodology for patients with both peripheral or "CNS" neurological diseases suffering from fatigue all have the same results - it's always blamed on "central activation failure", regardless whether the patient has CFS, MS, Amyotrophic lateral sclerosis, Guillain-Barré syndrome, Myasthenia Gravis, post-polio syndrome etc. (c) CNS feedback loops don't have to involve the brain, indeed these feedback loops can be responding to peripheral factors.

CNS driven is very different to their claim of no "objective physical signs".

There are indeed feedback loops. One key point is that there are two classes of CNS feedback loops, slow (latency) feedback that involves the brain that modulates effort and has a model of motor function, which is activated in parallel with the actual motor units (via efferent copy), and then the peripheral signals (golgi tendon, muscle spindles) are compared with the output of the model. If the brain senses a substantial decline in force at submaximal exertions, despite constant effort, this will be perceived as fatigue. (note that the model itself also has constant feedback to make sure it does not predict incorrectly - if it does predict incorrectly, then proprioceptive disorders will result!)

Since the brain is too slow for real-time feedback, there is also fast feedback that occurs between the spinal cord and a peripheral nerve. Thus "Central fatigue" feedback loops don't have to involve the brain at all, yet this is frequently assumed. The classical example of such feedback loops being involuntary reflexes. Another can be the limiting/smoothing of the amplitude of motor unit drive that cannot be maintained for more than brief spike under fatiguing conditions, due to metabolic kinetics or other disease-related reasons. This has the benefit that the overall (rate-coding) output will be less spiky under fatiguing conditions. (Unless someone decides to apply electrodes to the muscle.)
Example of the ITT technique being flawed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924481/

Anyway, the main claim was that there were no "objective physical signs", which is nonsense, because the fatigue can be measured, but they mistakenly only focus on maximal exertion and blame reductions on "central activation failure", which they like to blame on motivation, or other brain related behaviours, rather than than extracerebral factors and thus mistakenly claim there are no objective signs.
Secondly, dysfunction of CNS regulation of peripheral factors such as peripheral capillary tone can cause fatigue due to peripheral reasons, even though the underlying cause is still CNS damage.

 

Thank you for explaining, @Snow Leopard.

So then (b) should not be able to be used to indicate the one or the other cause (or better main cause). And with any feedback loops (c) between muscle and say spinal cord, maybe in MS, the interesting question arises why this would be, when e.g. MS is not too badly understood, and it´s a central disorder.

Yes, and this is rather my point. It seems that the words are not used in a good definition, and occasionally misused, if there is opportunity. But the basic differentiation is not difficult:

physiologically in the periphery - physiologically in the center - psychologically using the center

It becomes a bit more difficult when we distinguish symptoms and causes, and then it is muddled up quite profoundly. If one says that in MS or in a depression or in a fatique the motivation would be affected, one may better think twice if this calls for an psychologists (and if, in which respects). It should be recognized as ridiculous when one e.g. calls a psychologist because someone is drunken and doesn´t want to do anything, of when one has worked the whole day and is tired.