Fatigue in MS: can we measure it?

BACKGROUND: Fatigue is one of the commonest complaints in MS and is frequently reported as the most debilitating by MS’ers. Cognitive fatigue (CF) can be defined as decreased performance with sustained cognitive effort. The effectiveness of the Paced Auditory Serial Addition Task (PASAT) and the Computerized Test of Information Processing (CTIP) at detecting CF was examined in this study. Subjective fatigue was measured using the Fatigue Impact Scale (FIS). The relationship between objective and subjective fatigue was examined.

METHODS: 70 MS and 72 healthy controls (HC) completed the PASAT (3 second and 2 second), CTIP, and FIS as part of a larger battery.

“People find the 2 second PASAT very difficult! Trust me I have tried it myself.”

RESULTS: The MS and HCs performed worse on cognitively demanding tasks. Depending on methodology, PASAT performance varied between groups at the 3″ inter-stimulus interval (ISI) and the MS group showed greater susceptibility to CF as their ability to meet task demands declined as the task progressed. CTIP performance for both groups varied differently over time depending on task. The relationship between subjective and objective measures of fatigue varied depending on methodology, with PASAT generally correlating well with the Cognitive Dimension of the FIS.

CONCLUSIONS: The PASAT is a sensitive measure of CF in MS. Additional information is obtained with different scoring methods, with percent dyad scoring method being most sensitive to CF. The ability to detect a relationship between objective and subjective measures varied with methodology.

“I am doubt this work will be reproduced; although I wish it was. I started working on MS fatigue in the late 90’s and realised very soon that we don’t have a reliable and well-validated outcome measures to measure fatigue. In addition, fatigue is a normal physiological phenomenon and therefore defining what is pathological or excessive fatigue is a hard call. Despite this we need to get on top of fatigue as it is such a big problem for MS’ers. I am also convinced it is a major driver of unemployment and occupational under-achievement in early MS; MS’ers don’t necessarily have the cognitive zing to compete on a level playing field with “unaffected” people. Do any of you have any ideas on how to get on top of this problem?”

“In addition, we don’t have licensed treatments for MS-related fatigue. A lot of neurologists, including me, use drugs off-license; the commonest being Amantadine and Modafinil. The problem is that the majority of MS’ers find that their fatigue does not respond to these drugs.”

“Pharma, we need your help? There are a lot of pharmaceutical targets and potential small molecules to treat fatigue. We need one of you to invest in validating novel fatigue outcome measures and to then invest in some phase 2 exploratory trials.”

2 thoughts on “Fatigue in MS: can we measure it?”

  1. In your experience, how many of your patients respond to the current fatigue therapies? A third? More? Less?

  2. Re: "In your experience, how many of your patients respond to the current fatigue therapies? A third? More? Less?"~60% get some response to one of these drugs; the response is not 100%, but enough to help them function more "normally". Interestingly, some MS'ers with active disease and fatigue find their fatigue levels improve on DMTs, particularly the more active treatments (Natalizumab, Fingolimod and Alemtuzumab). Presumably the inflammation in the brain contributes to fatigue, by suppressing inflammation fatigue levels improve.

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