Brain cells

sneyz said:
Thought I'd bump this closer to the top of the pile now that the eMSN connection has surfaced:

Thread on "Three cases with chronic obsessive compulsive disorder report gains in wellbeing and function following rituximab treatment, 2024, Gallwitz et al"

Thread on "Rituximab for psychosis (double-blind RCT protocol)"

Comment by the second team on the works of the first team ("Three cases with chronic obsessive compulsive disorder report gains in wellbeing and function following rituximab treatment, 2024, Gallwitz et al")

Sorry if that's already been brought to attention elsewhere. There are some very honest comments in the thread on the quality of the scientific reasoning in the second paper. The data points might suddenly have become very interesting though.
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Ritux doesn’t work for ME/CFS as far as we know.
 
ScoutB said:
Even after years of this, I am always a little surprised by the range of symptoms my vyvanse dose reduces (which then return when it wears off). Flu-y symptoms, muscle aches, cognitive problems I have with fine motor skills and shakiness. I guess maybe this isn't too surprising because stimulants can reduce feelings/symptoms of sickness in other contexts too (e.g. the stimulant decongestant Pseudoephedrine can make people feel less flu-y when they have the flu). I wish we understood how this was happening though!
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I'm not on any stimulant but I do feel like whenever I'm stimulated I get less symptoms and feel like I'm able to do more without getting PEM. Now whether that's due to dopamine, adrenaline, cortisol or other neurotransmitters I do not know.

I think @Hutan has also mentioned this a few times in the past.

It's not really sustainable long-term as it usually does lead to an extended crash if I push it too much for too long. But it makes me feel better and able to do more than I otherwise could. Basically if I have very little stimulation and only try to rest I just start feeling worse and worse. So I need to balance stimulation and rest.

Edit: to clarify: with stimulated I generally mean things like excitement/novelty and other forms of mild stress/activation.
 
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Bethea said:
With migraine, the breakthrough was made when they took blood from the external jugular vein during a migraine attack and found high levels of CGRP. Interestingly this doesn't show up if you take blood from the body. I wonder if it would be worth doing this for pwME/CFS during PEM to see if anything showed up.

The researchers then infused CGRP into migraine patients and healthy controls and found it triggered an attack in the migraine patients but the healthy controls only had a mild headache.
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This is super interesting to me. My mom has had severe migraines for most of her life. Tried all the treatments and nothing worked. Until CGRP inhibitors.. she hasn't had a single episode since. Another disease that's been woefully underfunded. But on a more positive note it shows what can happen once targeted research happens and a drug gets developed that directly targets the disease-specific biology.

It would be so interesting if we would find any abnormal blood or brain measurement during PEM. There has to be something significant going on in the brain.
 
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What's kind of interesting is that on the other hand benzos also reduce my symptoms, allow me to do slightly more without getting PEM and helps me get into "recovery mode" after overexertion.

So that's an interesting juxtaposition between excitatory and inhibatory drugs..

Benzos might also tie into glutamate which I've seen mentioned a few times. As glutamate and GABA basically try to balance neuronal activity. I know many people get the wired but tired feeling. Could that involve excessive glutamate / neuronal activity? Benzos do help me calm the wired feeling in moments like that.
 
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My attempt at tying all of the above together, also including @hotblack's post. Might be all bogus and way too simplistic, please let me know ;)

I could see many similarities with migraine attacks and PEM. Apparantly in migraine the current view is that there's a certain threshold which when crossed triggers a migraine attack. What might also be similar is external and internal stimuli being the thing this threshold is about.
Now what seems different is that the threshold seems more way variable in migraine compared to PEM. Most ME/CFS patients roughly know what exertion will trigger PEM, while with migraine it seems more unpredictable.

So the way I would think about it then is that most types of exertion are generally correlated with internal and external stimuli. When pwME exert too much, it crosses our threshold for stimuli which then triggers PEM. Now of course I have no idea what pathways are involved. It also seems to further increase our sensitivity to stimuli (lowered threshold), which might be part of a loop prolonging the state.

Now back to dopamine: one could argue that stimulants (and their impact on dopamine) allows the brain to better handle all these stimuli through sensory gating or another mechanism. As far as I know people with ADHD see this benefit. When I'm stimulated I'm less sensitive to sound for example, while when not-stimulated or in PEM I'm way more sensitive to sound.

The link with GABA would be that due to its neural inhibitory effect it dampens the overwhelming effect of incoming stimuli.

Bottom line: might migraine be a helpful model for how PEM could work as a neurological issue?
And could an overload of internal and external stimuli be what triggers PEM?
 
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Bethea said:
The researchers then infused CGRP into migraine patients and healthy controls and found it triggered an attack in the migraine patients but the healthy controls only had a mild headache.
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Whenever I suggest that researchers try something similar (something that might make PWME temporarily worse) to identify reliable factors, it gets shot down because "researchers aren't allowed to do anything that might cause even temporary harm". I think it would be very helpful to learn that Interleukin-whichever reliably makes symptoms worse in 87% of PWME, or whatever. I'm guessing that the migraine study used levels that were normally encountered in humans, which seems to be the case in ME, since no one has found dramatically elevated levels of anything.
 
Bethea said:
With migraine, the breakthrough was made when they took blood from the external jugular vein during a migraine attack and found high levels of CGRP. Interestingly this doesn't show up if you take blood from the body. I wonder if it would be worth doing this for pwME/CFS during PEM to see if anything showed up.
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This is extremely interesting, and I would like to see it tried in ME/CFS. Am I off track, or does anyone else think this could be revealing? It seems like one of the easier ways of finding something reflective of brain pathology, at least.

There are one or two teams that have done home phlebotomy. Could they do this so no one has to intentionally induce PEM?
 
Verity said:
There are one or two teams that have done home phlebotomy. Could they do this so no one has to intentionally induce PEM?
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Sampling a jugular vein at home may not be that simple. If things go wrong you can get air embolism to the brain or dislodge a carotid artery plaque maybe. A radiologist or anaesthetist would know what to do but not a district nurse!

In principle it is a neat idea if we have a clear idea what chemicals to test for.
 
Verity said:
There are one or two teams that have done home phlebotomy. Could they do this so no one has to intentionally induce PEM?
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Currently working on seeing if this can be done (not jugular though). The hope would be that if someone has symptoms that span multiple organ symptoms (like runny nose and GI symptoms) then that's the most likely time that something might be found in the peripheral blood. It would be worthwhile to check that first. If there's nothing to find there, that would make a case for sampling the jugular, which like @Jonathan Edwards says would probably require a setup with access to doctors.
 
Unfortunately it probably wouldn't be feasible to do at home as the blood would need to be processed immediately. At least, for CGRP it needed to be processed within about 7 mins of being taken. I guess other chemicals might be longer?

In terms of how to go about doing this kind of research the person to talk to would be Prof Peter Goadsby from King's College London.
 
Jonathan Edwards said:
Sampling a jugular vein at home may not be that simple. If things go wrong you can get air embolism to the brain or dislodge a carotid artery plaque maybe. A radiologist or anaesthetist would know what to do but not a district nurse!

In principle it is a neat idea if we have a clear idea what chemicals to test for.
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Yikes! Good note. Wouldn’t want anything like that.
jnmaciuch said:
Currently working on seeing if this can be done (not jugular though). The hope would be that if someone has symptoms that span multiple organ symptoms (like runny nose and GI symptoms) then that's the most likely time that something might be found in the peripheral blood. It would be worthwhile to check that first. If there's nothing to find there, that would make a case for sampling the jugular, which like @Jonathan Edwards says would probably require a setup with access to doctors.
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I’m so glad to hear someone is looking into this! I get a runny nose and it does make me suspect something peripheral is going on. Do you have an idea of what sort of thing might show up if you’re able to do this?
Bethea said:
Unfortunately it probably wouldn't be feasible to do at home as the blood would need to be processed immediately. At least, for CGRP it needed to be processed within about 7 mins of being taken. I guess other chemicals might be longer?

In terms of how to go about doing this kind of research the person to talk to would be Prof Peter Goadsby from King's College London.
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That does complicate things. Maybe someone can reach out to Prof Goadsby. I would definitely just sound like a confused patient grasping at straws if I tried with my limited understanding!
 
Jonathan Edwards said:
Jonathan Edwards said:
If a cell seems to be doing something relevant to an illness - like prohibiting movement actions giving a sense of weakness or fatigue - then that presumably relates to its computing and so seems a useful clue. On the other hand the same function would not seem to help explain nausea or painfulness of light and sound. But we are not expecting the story to be easy I don't think. Moreover, my gut feeling is that if something is going wrong with brain cells it will involve more than one lot of cells getting into a confusion. I don't think we are expecting just loss of one cell type - which seems to be the easy explanation for narcolepsy. I think a brain aspect of ME/CFS is likely to involve potentially entirely reversible cross-talk between several cell types.
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When reading this post, I had to think of the Fujimoto et al. 2025 paper that showed the *systematic* increase in AMPA receptors.

From my understanding, these receptors can produce a lot of noise. But what if that noise can't be filtered out properly anymore? It's easy to imagine how that would play out in certain brain regions, e.g. visual snow and light sensitivity in the visual cortex or tinnitus and noise sensitivity in the part that processes audio.

But how would it play out in regions that for example control immune responses or upright posture or motor skills?
 
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fst said:
When reading this post, I had to think of the Fujimoto et al. 2025 paper that showed the "systematic* increase in AMPA receptors.

From my understanding, these receptors can produce a lot of noise. But what if that noise can't be filtered out properly anymore? It's easy to imagine how that would play out in certain brain regions, e.g. visual snow and light sensitivity in the visual cortex or tinnitus and noise sensitivity in the part that processes audio.

But how would it play out in regions that for example control immune responses or upright posture or motor skills?
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I think thiese are exactly the right sort of questions to ask. When working on RA my group used to sit and argue about possible mechanisms for two hours at a time (often with a few glasses of wine on a Friday evening). Over a period of months and years we built up a common understanding of what suggestions didn't work too well and what might be worth coming back to. It needed people with a range of different knowledge bases, which we came to share. If I was a neuroscientist now I would want to do the same here. I study brains but not at this level and I think I am probably too old to learn a lot of new stuff. But there are other people here moving forward on different aspects. We could do with some more neuroanatomy/ neurotransmitter scientists here. With luck we may get some joining in. When I am less preoccupied with other things I hope to explore the UCL neuroscience resources further.
 
Things I have been thinking. Do we think there are changes in the neurotransmitters themselves or changes in how they are processed? A lot of things seem to point to post synaptic so I guess receptors? But are we talking changes to the receptors or to some other part of the machinery of switching signals on/off? Are we looking at an epigenetic shift or something else? And exactly which receptors. We have hints at which cells but…?
 
hotblack said:
Things I have been thinking. Do we think there are changes in the neurotransmitters themselves or changes in how they are processed? A lot of things seem to point to post synaptic so I guess receptors? But are we talking changes to the receptors or to some other part of the machinery of switching signals on/off? Are we looking at an epigenetic shift or something else? And exactly which receptors. We have hints at which cells but…?
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Exactly!
 
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