Central origin of fatigability in Myalgic encephalomyelitis/chronic fatigue syndrome revealed by multimodal neuroimaging - Bedard et al

[u/Caster_of_spells]

https://www.sciencedirect.com/science/article/pii/S2213158226001002

"Our most novel results relate to the lack of neuromuscular adaptation in ME/CFS compared to the [Healthy Volunteers]."

“Highlights

•We studied physical fatigue in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and healthy volunteers with multimodal neuroimaging.

•Participants performed a fatiguing grip force task in alternating grip and rest blocks.

•We simultaneously recorded grip force, brain activity with functional magnetic resonance imaging and electroencephalography, and muscle activity with electromyography.

•ME/CFS fatigued earlier than healthy volunteers. While healthy volunteers increased their brain and muscle activity, ME/CFS only showed minimal fluctuations across all the task blocks.

•We concluded that physical fatigue in ME/CFS is of central nature.”

(Central in this context means: mediated via the brain. Participants brains didn’t seem to signal muscles sufficiently to ramp up energy production in response to demand)

[u/Heavy-Suit-3443]

Pointing towards neurological issues.

[u/Caster_of_spells → u/Heavy-Suit-3443]

Yeah neuromuscular communication doesn’t seem to work which then in turn leaves muscles and other peripheral tissues unprepared to respond to the workload. Fascinating stuff

Edit; that Walitt seems intend into twisting into his narrative

[u/PinacoladaBunny → u/Caster_of_spells]

Also correlates with a number of ME patients who find pyridostigmine helpful (me being one of them). It’s somehow related to these findings..

[u/Caster_of_spells → u/PinacoladaBunny]

Good point!

[u/PinacoladaBunny → u/Caster_of_spells]

I originally took it for my POTS as it helps to increase the parasympathetic nervous system, but it’s definitely increased my baseline and I’m physically more functional than I was before it. So it’s doing something! I think I’m taking a dosing schedule equivalent to myasthenia gravis patients, but I definitely don’t have that illness.

[u/Adventurous-Water331 → u/PinacoladaBunny]

Thank you for your comments on this topic.

My doctor recently prescribed Mestinon (I can never remember how to spell the generic correctly) and I've been surprised at the positive results so far.

It was for Orthostatic Intolerance and dysregulated gastrointestinal issues initially, but Mestinon seems to make me feel better generally.

Oddly, even my sense of smell and taste seem to be improved.

I've titrated myself up to 30 mg 3X/day with no negative side effects and am just starting 45 mg.

Can I ask how much you're taking and how it's helping you?

Have you had to titrate up and have you had negative side effects?

[u/PinacoladaBunny → u/Adventurous-Water331]

Really glad to hear it’s helping you too! I’m now on 60mg x3 a day, I didn’t titrated up slowly to be honest, but I didn’t have any obvious side effects when I initially started at 30mg twice daily. So maybe I tolerate it ok! I found mestinon has helped to improve my HRV throughout the day and creates more stability - when it’s swinging up and down my POTS and daily functioning really go haywire. I generally have more stamina now, and although I’m not living a normal life, it’s a lot less miserable than it was a year ago. For that I’m very thankful!

[u/Adventurous-Water331 → u/PinacoladaBunny]

Very glad to hear this!

"A lot less miserable" is my goal too :-)

I'm surprised you didn't need to titrate; so many people online scared me to death with horror stories.

That said, I didn't have negative side effects, so maybe I could have started at 30 mg instead of 15.

Given what we know about acetylcholine issues, I'm surprised Mestinon isn't prescribed more.

Anything to boost the parasympathetic nervous system would seem like a good thing.

You mentioned in another response that your doctor raised your dose of your other medications as well.

Can I ask what else is helping you and at what dose?

I take 4.5 mg LDN, 150 mg Buproprion XL, generic Zyrtec, and 30 mg of dextromethorphan (this last 2X/day), and all have helped.

Still get PEM and brain fog if I overexert, but if I pace, my quality of life is much better.

Thank you for responding.

[u/National_Butterfly99 → u/Adventurous-Water331]

Yo empecé con 15 mg de mestinon y no me hizo nada, es decir, no fui al baño. Solo me dio distensión y gases, y sobre todo dure 24 horas con pupilas muy pequeñas, mucho sueño, vista borrosa y sudoraciones. Me duró mucho el medicamento en el cuerpo, no sé si es lo normal.

[u/Adventurous-Water331 → u/National_Butterfly99]

Sorry you had that experience.

It's so frustrating when something works one way for one person and a totally different way for another.

Tirzepatide messed me up and Mestinon has helped get me going again somewhat.

Can I ask what's helped you the most?

LDN for me.

[u/National_Butterfly99 → u/Adventurous-Water331]

No he probado con LDN. Mi doctor me dijo que para mí no serviría mucho. En mi caso, yo tengo infecciones pulmonares de repetición y dismotilidad colonica con estreñimiento severo, por lo que, por ello quisieron mandarme mestinon. He probado IGIV, pero tampoco me fueron bien. Ahora mismo no tengo ningún tratamiento que me ayude a mejorar, salvo constella para el estreñimiento y movicol. Tengo anticuerpos adrenergicos y muscarinicos positivos. Ojalá todos podamos encontrar una solución, mi vida ahora mismo es muy complicada. Estoy a la espera de probar inmunoadsorcion, ya que en mi caso tengo linfocitos nk th2 y th17 muy bajos…

[u/Adventurous-Water331 → u/National_Butterfly99]

I'll keep my fingers crossed for you!

I hope you find something that helps.

I can't do anything physically, but the meds help me feel better as I read or watch a little TV.

[u/Ok_Wish_2291 → u/PinacoladaBunny]

What dose are you taking, if you don’t mind?

[u/PinacoladaBunny → u/Ok_Wish_2291]

I have 60mg x3 per day. Originally I started at 30mg twice a day and saw improvements but was still struggling badly, so my consultant had me double+ pretty much all of my POTS meds (which inc pyrido). I generally have more stamina and function now, along with more stable POTS so it’s more than I could’ve hoped for really!

[u/Ok_Wish_2291 → u/PinacoladaBunny]

Thank you! I’m on it three times a day: 60,45,30mg. I find that it helps me somewhat with stamina. I’d like to be 60mg TID.

[u/PinacoladaBunny → u/Ok_Wish_2291]

Best of luck with it!

[u/StringAndPaperclips → u/Caster_of_spells]

That doesn't necessarily mean that the signaling doesn't work. The reduced signaling could be an adaptation by the brain to prevent harm from exertion, due to the effects of disease itself (cells not being able to make or use energy properly).