Making Fatigue Real
Fatigue is like the Rodney Dangerfield of symptoms – it just gets no respect. The problem is the poor descriptive power of the word. It readily describes the everyday, manageable fatigue that most of the population regularly feels. That fatigue, though, has little relation to the pathological, functionally debilitating “fatigue” that people with chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), multiple sclerosis and some other diseases experience.
Studies indicate that the “fatigue” in these can be remarkably debilitating. Tony Komaroff’s large 1996 study indicated that people with ME/CFS were significantly more functionally impaired than people with congestive heart failure, type II diabetes mellitus, acute myocardial infarction, multiple sclerosis and hypertension. (Note that very severely ill ME/CFS patients were surely not included in this study.)
Self-tests and questionnaires to assess fatigue abound but are hardly trusted. What we really need is a test that objectively measures how much fatigue is present. Finding that has seemed kind of like the holy grail – a much desired goal but always seemingly out of reach. How do you measure such a seemingly subjective issue as fatigue?
One way is to identify a physiological attribute that changes depending on how much fatigue is present. The Japanese propose that a parasympathetic nervous system “collapse” that occurs after exertion in ME/CFS patients allows them to measure the amount of post-exertional malaise present.
Staci Stevens’s two-day exercise test certainly shows up the functional impairments caused by exercise in ME/CFS in spades but is expensive, takes two days to complete, and requires exercise. The two-day test is superb for proving disability and understanding the amount of activity an ME/CFS/FM patient’s system can handle. An ideal measure of fatigue that could be readily used in studies, though, would be non-invasive, cheap and easy to administer.
A cheap, easy-to-tadminister, non-invasive test which could be conducted using a wearable, no less, has actually been the focus of research lately.
The ramifications could be huge. Researchers could objectively determine if say, NK cell cytotoxicity or ATP output was actually correlated with increased fatigue. Or a clinical trial could determine more accurately how a drug or treatment protocol was affecting fatigue levels. Functional vs “non-functional” fatigue (depression?) could be identified.
The Eyes – A Window into Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM)
The eyes are turning out to provide a surprisingly effective window into fibromyalgia and chronic fatigue syndrome (ME/CFS). Non-invasive methods have been used to detect small fiber neuropathy in the eyes of fibromyalgia patients. Recently, researchers have been using computational eyeglasses to assess the association between fatigue and rapid eye movements called ‘saccades’.
Saccades refer to a quick, simultaneous movement of both eyes which occurs in a kind of jumping motion. These types of movements occur when our eyes scan their immediate environment or when we’re reading. (Could reduced eye movements be involved with the reading problems some ME/CFS/FM patients have?)
These movements occur very, very quickly but their speed, amplitude (distance traveled) and other factors can be measured.
The eye could be a window into the fatigue experienced in ME/CFS and FM.
The link between a decrease in rapid eye movements and fatigue was first seen in 1979. Since then, studies of healthy controls have consistently shown that reduced rapid eye movements are associated with fatigue and/or sleepiness. A 2012 and 2017 study found that people with multiple sclerosis – a severely fatiguing disorder – displayed significantly reduced eye movement velocity, amplitude and latency during a fatiguing task, relative to healthy controls. The authors of the 2012 study concluded that:
Assessment of peak velocity, amplitude and latency in a saccade fatigue task is a promising approach for quantifying fatigue in MS patients.
The studies suggest that measuring rapid eye movements or saccades could provide a measure of fatigue-limited functionality; i.e. the inability of the eyes to scan their surroundings properly.
Side Note – Central Fatigue, Chronic Fatigue Syndrome, Caffeine and Dopamine….
On a side note, studies have shown that, at least in healthy humans, caffeine, when taken after exercise, can reduce or prevent the reduction in rapid eye movements seen. This suggests that the normal fatigue associated with exercise is at least partially caused by what’s called “central fatigue” – or fatigue produced by the brain.
The idea of central fatigue actually has quite a history in ME/CFS. Years ago, Chaudhuri and Behan postulated that the fatigue occurring in chronic fatigue syndrome (ME/CFS) is “central” in nature. Their assertion was based on a number of findings (reduced motor performance, delayed central motor conduction, depressed cortical excitability, reduced ability to recruit muscles during exercise, reduced motor cortex activity), indicating that the inability of the brain to initiate motor activity was likely playing a major role in the fatigue found in ME/CFS.
In one remarkable finding, a researcher noted that the reduced muscle activation seen in CFS patients was similar to that seen in some stroke victims and ALS patients (!) (Schillings et. al. 2004).
Despite all the interesting findings, my recollection is that interest in motor cortex activation and reduced muscle recruitment in ME/CFS mostly died.
The interest in another part of Chaudhuri’s hypothesis has not, however. Behan and Chaudhuri suggested that problems relaying information from the basal ganglia to the motor cortices plays a key role in the fatigue in ME/CFS. Later studies by Miller have confirmed the basal ganglia problems in ME/CFS.
The basal ganglia connection is intriguing given recent studies which suggest that caffeine is able to reduce fatigue in part by increasing levels of norepinephrine and dopamine. Dopamine, it should be noted, is largely produced by the basal ganglia which Chaudhuri/Behan and Miller postulate is heavily involved in ME/CFS.
In conclusion, the eye studies suggest that similar brain issues to those studies may be occurring in ME/CFS and are responsible for the exertion-induced reduction in the saccades (rapid eye motions) found.
Back to the Eyes
The reduced eye movements seen after mental or physical exercise could, then, be due to problems in the brain.
The University of Mass. has begun a breast cancer fatigue study which will use computational eyeglasses to determine if fatigue levels in breast cancer are associated with declining rapid eye movements. Rachel Walker – a researcher associated with the study – explained why she hoped to validate a way to objectively assess the impact of fatigue on the eye movements.
“Often we ask breast cancer survivors to rate how fatigued they are feeling on a scale from 1 to 10. While this type of self-rating is critically important, it sometimes misses the functional aspect of the fatigue. The fact that someone not only feels fatigued – and what that might mean to them – but that the fatigue they are experiencing is having a measurable impact on their body.”
She described the wearable in the study (the computational eyeglasses) as being “low-cost”.
Could this upcoming study signal that the era of subjective questionnaires for fatigue is drawing to an end? Let’s hope so.
Wouldn’t that be great to be able to have an objective measure!! Keep us posted Cort!
If patients are also hypothyroid the medical advice is to avoid caffeine
That would gr8 then I could get people to know how I am suffering every day with this horrible thing .Mark.
This doesn’t seem to be measuring the post exertional exacerbation of multiple symptoms in people with ME, but just fatigue.
Good point, fatigue is just one symptom, aching all over with a flu like feeling mixed with a hangover and brain haze, are to me much worse than fatigue.
Absolutely. The flu-like symptoms are awful…
No, it doesn’t. However, even a test just to prove our fatigue is not normal would be fabulous. I am so sick of hearing “I feel tired to”, “oh, I’d love to spend the day in bed” aarrrgghh. If the fatigue we suffer is a medical ill and has a medical name added to it, then they might take some notice and realise we are not just TIRED! Thanks Cort for your wonderful blog.
I’ve been recently realizing that fatigue is the worst of all my symptoms. On my bad days, I feel like every cell in my body is being ripped in half in slow motion. Yet, most people have no understanding of how crippling this type of fatigue really is. It is frustrating to see how much more debilitated I am than my friend with MS, yet you get no support or sympathy. I look “normal”(ish) which doesn’t help. Thanks for the look into fatigue and how to define it.
How you measure the flu-like symptoms or other body sensations or pain I don’t know but an actual functional impairment caused by exertion is a pretty good start. It might be an analogue for some of the other symptoms. I remember Dr. Lerner saying that when the fatigue goes away; i.e. when the energy returns all the other symptoms get better.
This is imperative for people trying to get Social Security Disability..which i am told, i will most likely never get. The doctors have me listed as severe [but, can still work full time] yet do not say how this is disabling me. Proof, like mentioned, would be huge. It will take 15 years for it to become mainstream, though.
My eyes are puffy all around, lids sagged and vision blurred with double vision and sever light sensitivity, which can change drastically throughout the day and corresponding, when i developed, the pain, dizziness and gained 30lbs with no diet change and i have developed, new, onset Astigmatism??!!! It is inflammation and fluid! I was not like this before all this started and the doctors, all, even eye doctors, don’t get it! It is horrifying not getting help for this.
That’s true. But fatigue seems to be proportional to the severity (of PEM), at least in my experience. Thus, you could detect/measure PEM if you can measure the fatigue. That’s how I define and measure PEM in my reasearch in fact.
I’m actually not that enthusiastic about it. It think the test should be extremely sensitive and preferably very specific to prevent further abuse of patients. This doesn’t sound like the answer. On the other hand Ron Davis’s device sounds much more like a holy grail. Do you when(and if..) it could hit the market?
I know they’ll be working on it much more with the new money coming in. I don’t have any idea about the timeline though.
I think it’s teally interesting that the eyes are if interest. My husbands key indicator of how I’m going are my eyes. When I’m starting to head downhill he reckons my pupils become really tiny. I guess it types in somehow with increased light sensitivity.
We’ve also noticed that my perception of distance becomes very skewed when I’m not having a good day but am required to travel in the car. I get quite anxious because things seem much closer and faster than they are so I feel like we are having near misses all the time.
We have also noticed that whenever we meet other people with this illness we can see it in their eyes. We all tend to have this certain ‘look’. And I have noticed it in people’s photos too.
And I can see it in almost every photo I have of myself over the years.
Hi , can you explain that ‘ Look ‘
you see in the eyes please.
I have Fibromyalgia / Cf and my eyes always feel & look glazed.
I am always conscious of this as I know other people notice & have a questioning look in their eyes about me when I am up close speaking to them
I’m sorry that this causes you concern. I know what you are talking about, as I see it in my wife who has cfs. It befuddles me that people think she seems normal. She doesn’t look normal, just look at her friggin eyes! Again, sorry this distresses you. I imagine one of the reasons your eyes look like this is just because that’s what eyes if someone who is fatigued look like
I have mostly given up driving as I feel uncertain about distances and speed of other vehicles. Luckily my husband is a very patient man as I quite often panic when he is driving though he is a very good driver. I feel hard data will be invaluable for as we get older we may need home help etc and at least our need will be provable.
I don’t know about studies, but I was thinking such a device could be handy for home use–especially with making decisions about activities/rest. I could quickly imagine being able to say, when I have to say no again to some idea, that it would help to be able to say, my current fatigue level is ____. Instead of all the ridiculous things I say. I’m tired. I’m really really tired. But not being able to say anything scary: I’m so tired it feels like to breathe. Or I’m so tired my heart rate’s too high. (Both these examples lead to immediate questions about heart attack.)
The more hard data we can get the better. It may only measure one aspect of fatigue, but it is a start at quantifying fatigue.
So true. I am semi recovered after years and able to work. However my daughter recently succumbed to ME/CFS. Homeschooling and trying to explain why a former honors student is struggling to pass a basic online GED program to our board of education is frustrating. “Hard” data vs. my subjective explanations would be vindicating.
Wow…Must be so hard to see your daughter treated that way. It’s rough being a pioneer – which I guess is what we are – we are forging a trail through all sorts of difficulties so that others who come after us will have an easier path.
I can tell how fatigued I am by how many steps I take in a day. If I am feeling good it can be 4-5000, and on a very rare exceptional day 7-10,000. If I am sick, I do well to walk 2-3,000 steps a day. Many of us have devices with pedometers these days.
Pedometers are great…I wish we would see them in more studies.
That’s about the same amount as what I can do. The problem with using the total number of steps as the proxy for fatigue though, is that it may also depend on the exigent circumstances. You may end up doing more than you are inclined to when you have to run errands or someone’s visiting you. Or decide to take a walk despite fatigue to improve your mood or sleep. I’ve been monitoring for the past 2.5 years and the total number of steps hasn’t been a reliable measure for me.
That’s great news, if a neuropthamologist can distinguish ME from MS, depression and normal controls would be the goal. That could make diagnosis quicker. My neuro-opthamologist is a rock star. She is my only specialist now, neurology still doesn’ t recognize ME in Canada. She agreed to an informal study in her practice if enough evidence to separate these groups. Will see what she says. We have been keeping an eye on Claire Hutchinson and Dr. Badams work out of Leicaster. Here is a paper sponsored by ME Association UK., and others. http://irep.ntu.ac.uk/id/eprint/25859/1/221920_3205preprint.pdf ME UK are moving mountains in many ways that will help ME/patients around the world. Their new research collection is top notch and user friiendly. And of course our Cort Johnson, your are integral to our path, thank you.
Thanks. Really interesting stuff by Hutchinson and Badams. Thanks for sharing that.
“It is hypothesised that the effects of ME/CFS can be overcome briefly for
completion of saccades, but that continuous pursuit activity (accurately tracking a moving
object) even for a short time period highlights dysfunctional eye movement behaviour in
ME/CFS patients.”
I presume this is not referring to Rapid Eye Movement which occurs during sleep, but perhaps the reason humans can still see objects which are not moving, due to minute eye muscle movement.For instance cats eyes do not have this abilty which is why if a mouse keeps absolutely still, it does not get attacked, but the instant it moves WHAM.Is this constant minute eye muscle movement what is being referred to??
Another “aha” moment for me.When I was in High School many eons ago I constantly had tired eyes, was told by specialist nothing was wrong with my eyesight. Glasses were prescribed of course it didn’t help, now know why. Also another ” aha “, in the previous post someone mentioned discolouration around the mouth, my top lip has gone slightly greenish was wondering WTF so I researched and one cause in Chinese medicine may be lack of oxygen in the blood. I have a big problem with feeling short of breath and not getting enough air. Used to try deep breathing but that brings on panic type feeling and still can’t breathe. Thanks Cort and all for helping my understanding helps so much.
Forgot to mention eyes are playing up again,when tired have very blurry vision happens often. Another thing I have gleaned and realise now that from the time of pregnancies to menopause my symptoms were much less after age 54 got progressively worse (CFS,fibro,myofascial pain,a version of pots) Fun eh!
I was diagnosed with multiple sclerosis 1 month after I turned 50. My Grand-mum was 96 and had it since she was in her 20s. I was on Copaxone, the first year was daily and later I was on 40 mg, 3 times a week. It made a tremendous difference for me. Although the fatigue was what really gets to me. When I do too much, I do start to feel weak.There has been little if any progress in finding a cure or reliable treatment. My multiple sclerosis got significantly worse and unbearable because of my cognitive thinking.. Last year, i started on a natural multiple sclerosis Herbal therapy from Green House Herbal Clinic, i read a lot of positive reviews from patients who used the treatment and i immediately started on it. I had great relief with this herbal treatment. I am doing very much better now, no case of Cognitive thinking or memory Loss,, my multiple sclerosis condition is totally reversed.
I just looked up Green House Herbal Clinic and had a chat with a representative. Where do you live? I am in the USA. They do have a formula for CFS and will ship. However, it is quite pricey and I have no idea what is in the formula.
Did you get to talk to someone at the clinic? I am interested in their products, but wonder about the product itself and the price.
There were no reviews for the fatigue formula.
Could you explain your use of the term “cognitive thinking”? Thanks.
This sounds very interesting.Thanks Cort for bringing it to everyones attention. It made me think of car manufacturers….don’t they have devices which track the tiredness of drivers in their autonomous car versions. Probably far to over simplistic though?
At the Unrest screening in Berserkely last night I was telling researchers how another Incline survivor and I were taking advantage of sleeping better in the desert and recovering.
Apparently because we were getting good REM sleep.
Something in town that was disturbing our sleep was obviously
not present out in the GodForsakenDesert
In my worst bouts of ME/CFS fatigue I made a peculiar observation. I found that just mustering the ability to lift my index finger was difficult. That sleepy, exhausted, comatose feeling seemed to be rooted in my brain and nervous system. The connection between my willing the finger to lift and it lifting seemed to be inhibited or dampened by nervous system dysfunction. I also feel there is a muscle energy problem going on but the brain part of the fatigue seems to be the most pronounced.
Interesting. This jives with Cortene’s hypothesis as well.
Everything slows down in proportion to fatigue. After a month of trial, I found that my walking speed has 80% correlation to my subjective measure of fatigue. Monitoring the eye speed seems much easier though, logistically speaking: you don’t have to get up and walk, which is a challenge for severely ill patients.
Measuring fatigue with hrv doesn’t seem to work. I tried it with heart rate monitor and an android app and got practically zero correlation. Maybe you need a medical grade equipment for that, like the ones Japanese researchers used.
This just occured to me. Fitbit recently added API to allow access to the raw accelerometer data. I could fetch that and see if how fast I’m moving on average, or how much I fidget, correlates to the fatigue! Reading Cort’s blog often leads to an idea 🙂
🙂
That’s funny because many people such as specialist in medicine could say if I am in a good day or not just looking at my eyes. So, it is even esalily noticeable by an exercised praticien.
I notice in pictures of myself that my eyes are a dead giveaway to how sick I am. I see this in others with ME, too, that droopy look that makes me wonder how hard our muscles have to work to keep our eyes open at all.
Interesting -as increased cerebral fluid pressure – see the next blog – can affect the muscles of the eyes.
Has anyone used Green House Herbal that Carol Drali mentioned above? They have a formula for CFS. During an online chat I was told you only need to take if for several weeks and you will be healed. It costs $400.
That is Green House Herbal Clinic. ….typo in my last note
This concerns me. They are marketing an unknown substance (suspicious) that will cure us (more suspicious)? Why haven’t we heard success stories? I’ll pass.
I think I’ve had fibromyalgia for many years but was diagnosed approximately 5 years ago. I was working at Walmart and was just exhausted. Not the tiredness that sleep helps. I mean totally exhausted, with muscle pain. My primary doctor diagnosed fibromyalgia. He prescribed Cymbalta around 4 years ago. Cymbalta was approved for Fibromyalgia treatment. Although it did relieve some of the pain, I still suffered from fatigue. November 2017 my doctor started me on Green House Herbal Clinic fibromyalgia Herbal mixture, 7 weeks into treatment I improved dramatically. At the end of the full treatment course, the disease is totally under control. No case of fatigue, muscle pain,mood swings, or nervousness. Visit Green House Herbal Clinic official website I am strong again and able to go about daily activities.‌ This Herbal Formula is Incredible!! My life is back.
are you still fibro free? I just came across your comment. I have fibro for 10 years now and am looking for help other than meds.
Thank you
I’d love to have some tangible way (for dummies!) to ‘see’ how debilitated I actually am. I get so fed up that there are really a good number of people whom I no longer bother with. (How valuable is a friend anyway if they make no effort to comprehend?)