@Jonathan Edwards: If you wouldn't mind, I'd be grateful for your thoughts on this please. I'm not qualified to comment from a medical perspective, but from my own personal experience, tiredness and fatigue, though they can have a strong correlation, do not seem to me to be the same thing at all. As I see it, tiredness is when your brain is telling you you need to sleep. Of course fatigue can, and typically is, a common trigger for your brain to do this - but not the only trigger surely. I commented on this in ... Incidence of ME/cfs in a large prospective cohort of U.S, post #7 ... that there were periods many years ago when I used to suffer from quite severe tiredness, but not fatigue. I cannot help wondering if this is where a lot of confusion lies. I notice that quite a lot of research talks about the brain signalling fatigue, but how do researchers actually know if it is fatigue or tiredness that is being signalled? Is there a definitive objective test for this? Or is it back to patient questionnaires again? If it is questionnaire based, is a subject, or even researcher, necessarily going to know if the subject is really feeling very tired? ... or very fatigued? The two things can be ever so difficult to discriminate between. Indeed I suspect many patients (maybe researchers?) do not realise they are different. So are these researchers really researching people with fatigue at all, or potentially people with a condition that makes them feel extremely tired, even if they are not actually fatigued? And if their problem is tiredness rather than fatigue, but everyone involved in such trials believes they are researching fatigue ... no wonder it's all such a mess. I'm guessing that fatigue is very much about lack of useful energy being available where it is needed. No matter what a person's brain might tell them to do, they cannot defy the laws of physics and drum up energy that is not there. This feels to me the situation for ME sufferers. And I'm similarly guessing that tiredness is when your brain is telling you to sleep, irrespective of what useful energy your body may, or may not, have available. And maybe there are some conditions where a person's brain is insisting they feel tired, even if there is no apparent need. I wonder if this is where some misdiagnosed cases of ME occur. I mean - if someone feels very tired, but a questionnaire asks if the feel very fatigued, are they going to say Yes or No? And if some time later, they feel much less tired, and they are asked if they feel more/less/same fatigue as before, they are surely likely to say they feel less fatigued. Whereas in such a case, they would be really be less tired, but neither the subject or the researchers would know any different. Is asking about fatigue, actually a leading question that assumes fatigue, when it is not really known if the problem is tiredness or fatigue? And is the distinction between tiredness versus fatigue properly recognised?