Fatigue is one of the most disabling and poorly managed MS symptoms. In this Newsletter I try and explain why people with MS get fatigued and how to investigate and manage it.
Many of us with MS will remember how washed out we were during the time we had glandular fever / mono. If EBV (the mounting evidence suggests it is) is driving CNS-compartmentalised inflammation and relapses, then it is probably the main cause of fatigue. Getting rid of EBV (anti-viral) / getting it under control will likely have the most impact in reducing fatigue.
Over the last ten years or so (I’m ocd re reading MS research articles) the consensus among the top guns of the MS research field is that ebv has a central role in triggering / driving MS. Just one example:
We must be in touching distance of coming to some sort of definitive view and a way forward. Will the Sizomus trial tell us anything about the role of EBV in MS?
Since I use Methylphenidate twice a day, I have my life back a little bit.
Without Methylphenidate I have microsleeps from 11 a.m. and my day is worth nothing. The advantage of Methylphenidate and not falling asleep during the day is that my sleep is more compact at night and I do not wake up and lie awake for hours and fall asleep again.
Additional Comment: When I am not taking Methylphenidate my ESS score is 16. With Methylphenidate my ESS is 3. Symmetrel is not working for me. Have had multiple PSGs at the sleep center, found no sleep disorders. When I use Methylphenidate I also suffer less from heavy legs.
Great article, Dr G! I try to exercise 4-5 times a week and also use a CPAP, along with Ritalin. I am a 51y/o male diagnosed 30 years ago EDSS of 6.5 with significant brain atrophy. I shudder to think how much worse my fatigue would be if I didn't treat with proper sleep and exercise. I also take fampridine which hasn't helped with walking speed but may still have a positive effect on fatigue by improving conduction in the brain.
My fatigue has been the most disabling that I have ever experienced over the last month or so. Perhaps a result of the perfect storm - stress levels have been high, previous relapse symptoms have reoccurred, weather temperatures have been high and second AZ vaccination in amongst all this! Had bloods checked by neurology dept (am on Tysabri so part of regular infusion checks) and at GP. Nothing obvious coming up except slightly low platelets and urine check indicated a non-symptomatic UTI. No sign of inflammation detected. So it's just a case of working through it till it improves?
Also wondered if you might be able to address hearing loss associated with MS. I was tested and found hearing loss around 9 years before MS diagnosis ( but also had other MS symptoms present pre-diagnosis). Wear hearing aids to help but find that, besides loss of ability to hear at certain frequencies, that even when I can hear volume well enough I have difficulty making out what is being said in conversations ( not a typical hearing problem I presume?). Is there any kind of diagnostic test that might assess the auditory nerve performance similar to the evoked potentials test for the optic nerves?
Hearing impairment as an MS symptom is apparently relatively rare but no one seems to be engaged with following up with this. It can be quite disruptive as it impairs your ability to socialise and communicate so can have a significant impact on quality of life
My experience - testing for thyroid comorbidity is not sufficient in most countries.
A quick TSH and if you are lucky, free T4.
However in the presence of DIO1 and DI02 genetic variances which reduce conversion to free T3 - the hormone that actually does the work - these numbers can be fine for a long time.
Given that the main symptoms of low T3 is temperature sensitivity and fatigue (sounds like MS!), I would really encourage free T3 testing as well.
I’m completely disabled without my T3 containing thyroid meds. Without, my T3 drops to low normal or below. Even low normal, I can barely move.
I would especially consider this with patients who have low body temperatures - hot weather is that much hotter and disabling when your temp is 95 F (35 C).
Yes, I couldn't agree with you more. I have a few patients with thyroid problems post-alemtuzumab who have T3 hypothyroidism with normal T4 levels. The problem with this issue is that the T3 tests are often restricted to endocrinology requests only, i.e. Dr Joe Soap can't necessarily order T3 levels. The latter depends on the healthcare system you work in. You have to realise T3-hypothyroidism is actually quite rare and is quite a complicated issue.
There are three enzymes catalyzing deiodination from T4 to T3; type 1 (D1), type 2 (D2) and type 3 (D3) iodothyronine deiodinases. D1 occurs largely in the liver and kidney and clears rT3 from the blood and contributes to the production of plasma T3. D2 occurs in the central nervous system, pituitary, brown adipose tissue and muscle and, generally, its expression responds to changes in thyroid state and responds to physiological needs. D3 occurs in foetal tissues and in adult brain tissue. and can be induced under certain pathological conditions such as critical illness or with certain cancers. D2 and D3 locally modify thyroid hormone bioactivity at the tissue level that is independent of blood thyroid hormone concentrations.
This is why the interpretation of T3 levels are generally left up to endocrinologists.
One doesn’t get a referral to an endocrinologist until T4 is out of whack. We waste precious years untreated.
I’ve been put on every MS fatigue and too many sleep meds. Imagine my surprise when two weeks in on a T3-containing regimen (once my thyroid died “enough”, sleep and fatigue started to resolve. Very specific sleep dysfunction/disorder I had for at least five years.
There was a trial I’ve uncovered using T3 for remyelination. Participants had less fatigue. Is it remyelination? Or is it juice for a battery that has none due to lack of conversion?
We don’t know because of poor testing. I would love to carry out this research project.
Loving these symptom focused articles - incredibly accessible and very useful, especially to the many of us who are pretty much left to manage our disease ourselves.
Not only HSCT. I have seen this natalizumab and alemtuzumab as well. The fatigue takes longer to improve post-alemtuzumab. But again this depends on the stage of the disease; if you wait too long and acquire too much damage then you can't reverse some of the mechanisms driving MS-related fatigue.
I use THC-oil in the evening,, great for Spasticity and I almost never wakeup in the middle of the evening. When I do wakeup I fall asleep so much faster. This helped me a lot with my fatigue. Now the following might not help for most pwms, but for me it helps when I eat plenty of complex carbs. I am in the diet game for 2 years now and tried a lot of diets and I seem to do best on 3 meals with complex carbs. I do fast for 16 hours every day. So if you notice your getting fatigued from fatty meals/ on Keto diet, you can give the opposite a try. Not drinking more than 3 cups of coffee before 12 am also helps, bit obvious but a caffeine dip is no good when you have MS. When I do get fatigued it is always between 11:30 am and 4pm. I can feel pretty fatigued at say 3pm and feel almost energised at 5pm. Really crazy, please share if you experience the same and or have an explanation.
Mixed results from what I've read. Might only work through not noticing the Spasticity that much. Not covered by insurance in Holland so evidence would be great. Would love to try sativex if someone else is paying it. Being mildly high is not ideal most of the time.
Many of us with MS will remember how washed out we were during the time we had glandular fever / mono. If EBV (the mounting evidence suggests it is) is driving CNS-compartmentalised inflammation and relapses, then it is probably the main cause of fatigue. Getting rid of EBV (anti-viral) / getting it under control will likely have the most impact in reducing fatigue.
Yes, possibly but this is a hypothesis that needs to be tested. This is why we are doing clinical trials of anti-EBV agents in MS. Watch this space.
Over the last ten years or so (I’m ocd re reading MS research articles) the consensus among the top guns of the MS research field is that ebv has a central role in triggering / driving MS. Just one example:
https://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwifqYyw56PyAhXIVsAKHezRBN4QFnoECAUQAw&url=https%3A%2F%2Fwww.researchgate.net%2Fpublication%2F338009575_Epstein-Barr_Virus_in_Multiple_Sclerosis_Theory_and_Emerging_Immunotherapies&usg=AOvVaw2QpmszPTqYfnl1Ezjl_3kB
We must be in touching distance of coming to some sort of definitive view and a way forward. Will the Sizomus trial tell us anything about the role of EBV in MS?
Since I use Methylphenidate twice a day, I have my life back a little bit.
Without Methylphenidate I have microsleeps from 11 a.m. and my day is worth nothing. The advantage of Methylphenidate and not falling asleep during the day is that my sleep is more compact at night and I do not wake up and lie awake for hours and fall asleep again.
It's not a miracle cure, but I'm happy with it.
Additional Comment: When I am not taking Methylphenidate my ESS score is 16. With Methylphenidate my ESS is 3. Symmetrel is not working for me. Have had multiple PSGs at the sleep center, found no sleep disorders. When I use Methylphenidate I also suffer less from heavy legs.
Great article, Dr G! I try to exercise 4-5 times a week and also use a CPAP, along with Ritalin. I am a 51y/o male diagnosed 30 years ago EDSS of 6.5 with significant brain atrophy. I shudder to think how much worse my fatigue would be if I didn't treat with proper sleep and exercise. I also take fampridine which hasn't helped with walking speed but may still have a positive effect on fatigue by improving conduction in the brain.
My fatigue has been the most disabling that I have ever experienced over the last month or so. Perhaps a result of the perfect storm - stress levels have been high, previous relapse symptoms have reoccurred, weather temperatures have been high and second AZ vaccination in amongst all this! Had bloods checked by neurology dept (am on Tysabri so part of regular infusion checks) and at GP. Nothing obvious coming up except slightly low platelets and urine check indicated a non-symptomatic UTI. No sign of inflammation detected. So it's just a case of working through it till it improves?
Also wondered if you might be able to address hearing loss associated with MS. I was tested and found hearing loss around 9 years before MS diagnosis ( but also had other MS symptoms present pre-diagnosis). Wear hearing aids to help but find that, besides loss of ability to hear at certain frequencies, that even when I can hear volume well enough I have difficulty making out what is being said in conversations ( not a typical hearing problem I presume?). Is there any kind of diagnostic test that might assess the auditory nerve performance similar to the evoked potentials test for the optic nerves?
Hearing impairment as an MS symptom is apparently relatively rare but no one seems to be engaged with following up with this. It can be quite disruptive as it impairs your ability to socialise and communicate so can have a significant impact on quality of life
Yes, MS can affect hearing and it does it in quite subtle ways. I will have to do a separate Newsletter on this.
That would be really interesting and helpful - thanks!
My experience - testing for thyroid comorbidity is not sufficient in most countries.
A quick TSH and if you are lucky, free T4.
However in the presence of DIO1 and DI02 genetic variances which reduce conversion to free T3 - the hormone that actually does the work - these numbers can be fine for a long time.
Given that the main symptoms of low T3 is temperature sensitivity and fatigue (sounds like MS!), I would really encourage free T3 testing as well.
I’m completely disabled without my T3 containing thyroid meds. Without, my T3 drops to low normal or below. Even low normal, I can barely move.
I would especially consider this with patients who have low body temperatures - hot weather is that much hotter and disabling when your temp is 95 F (35 C).
EBV and thyroid - also closely related.
Yes, I couldn't agree with you more. I have a few patients with thyroid problems post-alemtuzumab who have T3 hypothyroidism with normal T4 levels. The problem with this issue is that the T3 tests are often restricted to endocrinology requests only, i.e. Dr Joe Soap can't necessarily order T3 levels. The latter depends on the healthcare system you work in. You have to realise T3-hypothyroidism is actually quite rare and is quite a complicated issue.
There are three enzymes catalyzing deiodination from T4 to T3; type 1 (D1), type 2 (D2) and type 3 (D3) iodothyronine deiodinases. D1 occurs largely in the liver and kidney and clears rT3 from the blood and contributes to the production of plasma T3. D2 occurs in the central nervous system, pituitary, brown adipose tissue and muscle and, generally, its expression responds to changes in thyroid state and responds to physiological needs. D3 occurs in foetal tissues and in adult brain tissue. and can be induced under certain pathological conditions such as critical illness or with certain cancers. D2 and D3 locally modify thyroid hormone bioactivity at the tissue level that is independent of blood thyroid hormone concentrations.
This is why the interpretation of T3 levels are generally left up to endocrinologists.
One doesn’t get a referral to an endocrinologist until T4 is out of whack. We waste precious years untreated.
I’ve been put on every MS fatigue and too many sleep meds. Imagine my surprise when two weeks in on a T3-containing regimen (once my thyroid died “enough”, sleep and fatigue started to resolve. Very specific sleep dysfunction/disorder I had for at least five years.
There was a trial I’ve uncovered using T3 for remyelination. Participants had less fatigue. Is it remyelination? Or is it juice for a battery that has none due to lack of conversion?
We don’t know because of poor testing. I would love to carry out this research project.
Loving these symptom focused articles - incredibly accessible and very useful, especially to the many of us who are pretty much left to manage our disease ourselves.
The best intervention for treating fatigue seems to be HSCT. Some people have their scores on fatigue scales go from max to normal levels.
Not only HSCT. I have seen this natalizumab and alemtuzumab as well. The fatigue takes longer to improve post-alemtuzumab. But again this depends on the stage of the disease; if you wait too long and acquire too much damage then you can't reverse some of the mechanisms driving MS-related fatigue.
Thank you for this it’s excellent.
I use THC-oil in the evening,, great for Spasticity and I almost never wakeup in the middle of the evening. When I do wakeup I fall asleep so much faster. This helped me a lot with my fatigue. Now the following might not help for most pwms, but for me it helps when I eat plenty of complex carbs. I am in the diet game for 2 years now and tried a lot of diets and I seem to do best on 3 meals with complex carbs. I do fast for 16 hours every day. So if you notice your getting fatigued from fatty meals/ on Keto diet, you can give the opposite a try. Not drinking more than 3 cups of coffee before 12 am also helps, bit obvious but a caffeine dip is no good when you have MS. When I do get fatigued it is always between 11:30 am and 4pm. I can feel pretty fatigued at say 3pm and feel almost energised at 5pm. Really crazy, please share if you experience the same and or have an explanation.
Not convinced that THC-oil helps. This would have to be tested in clinical trials.
Mixed results from what I've read. Might only work through not noticing the Spasticity that much. Not covered by insurance in Holland so evidence would be great. Would love to try sativex if someone else is paying it. Being mildly high is not ideal most of the time.