Objective assessment of diverse types of MS related fatigue and fatiguability

[Woolie]

Interesting find, @MSEsperanza.

Re the Stoll paper: I was reading along, thinking it was a pretty good way of assessing cognitive fatigability. Then hope turned to disappointment when I got to the bit where they interpret a null result (lack of a significant correlation) as positive evidence that fatigue and fatigability are independent measures.

Here is the bit where it all seems to unravel (in bold):

Reaction time performance was significantly prolonged after the cognitive
load-based intervention. Furthermore, the participants indicated a significantly reduction in well-being afterward. There were no significant
changes in reaction time performance or well-being due to the relaxation intervention. There was no significant correlation between the reduction in well-being and the reaction time performance decline, although performance and well-being were similarly affected by load..

What they seem to have here is two variables that respond similarly to a single manipulation, suggesting they are very tightly related. The fact that they don't directly correlate with one another is probably because each measure captures different kinds of "noise" (RT effects may vary depending on a person's overall cognitive capacity - cognitive "reserve" - whereas self-report measures will be affected by personality variables). They could still be tapping into the same core construct - this seems very likely to me, given that they are both sensitive to cognitive load.

I'm also a bit unclear what the "well-being" measure might be, and my German is not good enough for me to read the original. Sounds very woolly, however (no pun intended!).

 

[MSEsperanza]

I'm also a bit unclear what the "well-being" measure might be,

I don't have access to the pay-walled paper, so don't know either.

I'm not sure if the German noun 'Befinden' that is used in the original (abstract) has an equivalent in the English language. It can mean 'Wohlbefinden' which means well-being in the sense of quality of life. It can also mean the subjective perception of one's emotional and physical state.

I guess the latter is what was asked in the questionnaire -- some cognitive, emotional and physical symptoms which the investigators associate with feeling fatigued.

Google translate of the German wikipedia entry on 'Befinden' see here.

 

[MSEsperanza]

Just leave some references to more recent reviews here -- not read yet but skimming through the results I get the impression there hasn't been any progress in the conceptualization of research into MS related fatigue and fatigability since I started the thread?

[Edit: However, more promising are some papers exploring exploring objective measurements of fatigability -- see the paper posted two post below.]

Adibi I, Sanayei M, Tabibian F, Ramezani N, Pourmohammadi A, Azimzadeh K. Multiple sclerosis-related fatigue lacks a unified definition: A narrative review. J Res Med Sci. 2022 Mar 17;27:24. doi: 10.4103/jrms.jrms_1401_20. PMID: 35419061; PMCID: PMC8995308.
Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995308/

Just did a very quick search for recent papers after stumbling across this (I think annoying) paper from 2016:

Veauthier C, Hasselmann H, Gold SM, Paul F. The Berlin Treatment Algorithm: recommendations for tailored innovative therapeutic strategies for multiple sclerosis-related fatigue. EPMA J. 2016 Nov 24;7(1):25. doi: 10.1186/s13167-016-0073-3. PMID: 27904656; PMCID: PMC5121967.

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121967/


And I'm curious to know whether the two articles discussing potential placebo effects of treatments for MS related fatigue take into account only placebo effects of drugs or also of the apparently always recommended cognitive-behavioral interventions and exercise?

Unfortunately, the first papers are paywalled:


1) Howard D, Galetta K. Rethinking the algorithm for fatigue management in MS -- how the placebo effect can confound clinical expertise. Mult Scler Relat Disord. 2022 Jul 2;65:104021. doi: 10.1016/j.msard.2022.104021. Epub ahead of print. PMID: 35810722.

No abstract available but a 'Highlights' section:

• Patients with multiple sclerosis (MS) frequently complain of fatigue
• Neurologists use non-FDA approved prescription drugs early in fatigue treatment
• These types of drugs may be more dangerous than and only as effective as placebo
• Physicians may underrecognize the placebo effect in MS fatigue treatment
• Doctors should use coenzyme Q10 earlier and avoid prescription drugs for MS fatigue

2) Bourdette D. Are drugs for multiple sclerosis fatigue just placebos? Lancet Neurol. 2021 Jan;20(1):20-21. doi: 10.1016/S1474-4422(20)30415-4. Epub 2020 Nov 23. PMID: 33242420.

2) is a comment on:

Nourbakhsh B, Revirajan N, Morris B, Cordano C, Creasman J, Manguinao M, Krysko K, Rutatangwa A, Auvray C, Aljarallah S, Jin C, Mowry E, McCulloch C, Waubant E. Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial. Lancet Neurol. 2021 Jan;20(1):38-48. doi: 10.1016/S1474-4422(20)30354-9. Epub 2020 Nov 23. PMID: 33242419; PMCID: PMC7772747.

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772747/

Edit: See also the following two posts.

Edit 2 to fix links.

 

[MSEsperanza]

Adding to the above --

Mij almost simultaneously posted another paper relevant to this thread:

The pathophysiology of motor fatigue and fatigability in multiple sclerosis, 2022, Robert Patejdl
https://www.frontiersin.org/articles/10.3389/fneur.2022.891415/full

Multiple Sclerosis (MS) is a heterogeneous immune mediated disease of the central nervous system (CNS). Fatigue is one of the most common and disabling symptom of MS. It interferes with daily activities on the level of cognition and motor endurance. Motor fatigue can either result from lesions in cortical networks or motor pathways (“primary fatigue”) or it may be a consequence of detraining with subsequent adaptions of muscle and autonomic function.

Programmed exercise interventions are used frequently to increase physical fitness in MS patients. Studies investigating the effects of training on aerobic capacity, objective endurance and perceived fatigability have yielded heterogenous results, most likely due to the heterogeneity of interventions and patients, but probably also due to the non-uniform
pathophysiology of fatigability among MS-patients.

The aim of this review is to summarize the current knowledge on the pathophysiology of motor fatigability with special reference to the basic exercise physiology that underlies our understanding of both pathogenesis and treatment interventions.

 

[MSEsperanza]

This one sounds a bit more promising at least with regard to the need for a more precise definition and assessment of diverse types and dimensions of fatigue, and exploring objective measurements of fatigability:

Block VJ, Bove R, Nourbakhsh B. The Role of Remote Monitoring in Evaluating Fatigue in Multiple Sclerosis: A Review. Front Neurol. 2022 Jun 27;13:878313. doi: 10.3389/fneur.2022.878313. PMID: 35832181; PMCID: PMC9272225.


Abstract

Fatigue is one of the most common multiple sclerosis (MS) symptoms. Despite this, monitoring and measuring fatigue (subjective lack of energy)– and fatigability (objectively measurable and quantifiable performance decline)– in people with MS have remained challenging.

Traditionally, administration of self-report questionnaires during in-person visits has been used to measure fatigue. However, remote measurement and monitoring of fatigue and fatigability have become feasible in the past decade. Traditional questionnaires can be administered through the web in any setting. The ubiquitous availability of smartphones allows for momentary and frequent measurement of MS fatigue in the ecological home-setting. This approach reduces the recall bias inherent in many traditional questionnaires and demonstrates the fluctuation of fatigue that cannot be captured by standard measures.

Wearable devices can assess patients' fatigability and activity levels, often influenced by the severity of subjective fatigue. Remote monitoring of fatigue, fatigability, and activity in real-world situations can facilitate quantifying symptom-severity in clinical and research settings.

Combining remote measures of fatigue as well as objective fatigability in a single construct, composite score, may provide a more comprehensive outcome. The more granular data obtained through remote monitoring techniques may also help with the development of interventions aimed at improving fatigue and lowering the burden of this disabling symptom.


Full text via free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272225/

Edit: Looking at the references, the Schmieder Kliniken/ Lurija Institute's research on tools to measure motor fatigue (see opening post) currently doesn't seem to be relevant.