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

[Andy]

Objectives
To identify the experiences that result from MS-related fatigue (MSRF) through a systematic review and thematic synthesis of qualitative literature.

Design
The thematic synthesis was undertaken in three stages: (1) a systematic review of the literature, searching relevant databases from their inception to March 2016. (2) A critical appraisal of included studies, and (3) a double blind 2-phase synthesis of results was undertaken.

Setting
Participants were included from articles using primary and secondary care settings.

Participants
The synthesis included nine articles that incorporated a total of one hundred and fifty two participants (103 females and 49 males) in the review.

Results
No articles were excluded following critical appraisal. Two major themes were synthesised: (1) biopsychosocial experiences of fatigue, which illustrated the physical, cognitive and social challenges patients experience and (2) experiences that alter the impact of fatigue including the strategies individual employ to help manage fatigue. These major themes were further split into five subthemes.

Limitations
Only the most common experiences of MSRF were identified. Findings did not break down results by key demographics e.g. disease type. Only English language studies were included.

Conclusion
Physiotherapists are able to support the management by: (a) having a greater understanding of MSRF and (b) being able to help patients manage the factors that influence it.

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

 

[Snow Leopard]

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.

MSRF and its multi-dimensional nature it is poorly understood [10]. The main reasons for this lack of understanding include that; (a) the pathogenesis is unknown (we do not consider this in more detail in this paper) [2,3,4], (b) the experience of fatigue for individuals with MS is different to that experienced by the healthy population [11], (c) the subjective experience of fatigue does not correlate to objective physical signs, and (d) two of the most utilised scales that measure fatigue (Fatigue Severity Scale; FSS and Modified Fatigue Impact Scale; MFIS) have been identified as insensitive and unresponsive to changes in a patients fatigue level [12]. MSRF is therefore known as an invisible symptom [13].

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.

Greater understanding of MSRF is required to stop physiotherapists relating their own experiences of fatigue to how the patients are feeling [25]. Educating both family members or carers will allow patients to work in a partnership with someone else which can promote coping [35]. Physiotherapists need to manage psychological factors like a sense of control or depression and mood [29]. Physiotherapists should consider using educational programs that incorporate mindfulness, energy conservation and fatigue management strategies [29, 30, 38]. The clinical assessment of MSRF must be undertaken with a measure that is of most relevance to the fatigue experience by the individual and must include broader factors, which are associated with secondary fatigue (e.g., mood and sleep) [39]

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.

 

[spinoza577]

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)...

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.

 

[Snow Leopard]

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

I guess supramaximal twitch analysis indicates peripheral causes to indeed feel fatiqued, but is negative here. So you say, that this is false negative.

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.

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.

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.

 

[spinoza577]

Thank you for explaining, @Snow Leopard.

(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.

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.

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

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.