Do catatonia and ME/CFS have pathophysiological similarities?

leokitten

leokitten

Senior Member (Voting Rights)
A friend of mine on PR mentioned this to me, so all credit goes to him (you know who you are!).

I had no idea of the theory that catatonia and ME/CFS might share pathophysiological features. Catatonia is not always caused by psychiatric disorders, there are neurobiological and immune causes too.

Drugs like lorazepam and aripiprazole can be effective in treating catatonia. In fact, a lorazepam challenge is used as a diagnostic tool for the condition. It might just be a coincidence, but as many of you know, there is anecdotal evidence that lorazepam and aripiprazole seem to improve ME symptoms in many people, even in very severe cases.

Here’s a Twitter thread discussing the possible similarities and a Lancet review on catatonia and the immune system.

 
Last edited:
To me, it seems like catatonia is more like a symptom or group of symptoms than a disease. A sort of shorthand for ‘someone not acting normally’.
Doctors can diagnose someone as catatonic if they have any three of these signs:
  • Not responding to other people or their environment
  • Not speaking
  • Holding their body in an unusual position
  • Resisting people who try to adjust their body
  • Agitation
  • Repetitive, seemingly meaningless movement
  • Mimicking someone else’s speech
  • Mimicking someone else’s movements
Click to expand...
I don't think I have any of those signs, although no one has tried to 'adjust my body' lately. It's entirely likely that I might resist that, and tick the 'agitation' box too if they persisted. It all sounds a bit 19th century to me.

My understanding of lorazepam is that it's a sedative - it calms the person down. To me, it makes as much sense treating someone with catatonia with a sedative as treating someone with pain with a pain-killer. In both cases, the person might feel happier and is probably a lot less trouble to have around, and so it might be helpful, but the root cause of the problem is not addressed.
 
Last edited:
Hutan said:
To me, it seems like catatonia is more like a symptom or group of symptoms than a disease.
Click to expand...

Well it’s a clinical syndrome just like ME/CFS. Your description above fits for ME/CFS too, we don’t know what the underlying condition(s) or illness are, and there could be multiple. Just like with ME, biological abnormalities have been found in catatonia.
 
Hutan said:
I don't think I have any of those signs, although no one has tried to 'adjust my body' lately. It's entirely likely that I might resist that, and tick the 'agitation' box too if they persisted. It all sounds a bit 19th century to me.
Click to expand...

Sorry if I’m not clear, I’m not meaning if symptoms are shared between the two syndromes, but if there might be some underlying pathophysiological similarities, particularly as ME becomes more severe.

Catatonia is believed to involve disturbances in GABA, glutamate, and dopamine signalling. Maybe there is something to be learned from this wrt to ME pathophysiology and why lorazepam seems to temporarily help in ME too.
 
GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and behavioral alterations. Ramirez et al. Brain Behav Immun (2016)
Objective: Psychosocial stress is associated with altered immunity, anxiety, and depression. Repeated social defeat (RSD), a model of social stress, triggers egress of inflammatory myeloid progenitor cells (MPCs; CD11b(+)/Ly6C(hi)) that traffic to the brain, promoting anxiety-like behavior. In parallel, RSD enhances neuroinflammatory signaling and long-lasting social avoidant behavior. Lorazepam and clonazepam are routinely prescribed anxiolytics that act by enhancing GABAergic activity in the brain. Besides binding to the central benzodiazepine binding site (CBBS) in the central nervous system (CNS), lorazepam binds to the translocator protein (TSPO) with high affinity causing immunomodulation. Clonazepam targets the CBBS and has low affinity for the TSPO. Here the aims were to determine if lorazepam and clonazepam would: (1) prevent stress-induced peripheral and central inflammatory responses, and (2) block anxiety and social avoidance behavior in mice subjected to RSD.

Methods: C57/BL6 mice were divided into experimental groups, and treated with either lorazepam (0.10mg/kg), clonazepam (0.25mg/kg) or vehicle (0.9% NaCl). Behavioral data and tissues were collected the morning after the last cycle of RSD.

Results: Lorazepam and clonazepam were effective in attenuating mRNA expression of CRH in the hypothalamus and corticosterone in plasma in mice subjected to RSD. Both drugs blocked stress-induced levels of IL-6 in plasma. Lorazepam and clonazepam had different effects on stress-induced enhancement of myelopoiesis and inhibited trafficking of monocytes and granulocytes in circulation. Furthermore, lorazepam, but not clonazepam, inhibited splenomegaly and the production of pro-inflammatory cytokines in the spleen following RSD. Additionally, lorazepam and clonazepam, blocked stress-induced accumulation of macrophages (CD11b(+)/CD45(high)) in the CNS. In a similar manner, both lorazepam and clonazepam prevented neuroinflammatory signaling and reversed anxiety-like and depressive-like behavior in mice exposed to RSD.

Conclusion: These data support the notion that lorazepam and clonazepam, aside from exerting anxiolytic and antidepressant effects, may have therapeutic potential as neuroimmunomodulators during psychosocial stress. The reversal of RSD-induced behavioral outcomes may be due to the enhancement of GABAergic neurotransmission, or some other off-target effect. The peripheral actions of lorazepam, but not clonazepam, seem to be mediated by TSPO activation.
Click to expand...
 
Catatonia is not in any way reminiscent of ME. Catatonia is usually associated with psychosis and immediately strikes one as strange and suggestive of major disturbance in brain function. It is not in any way like 'being too weak to move' nor 'not wanting to be moved' or anything remotely related to a situation we can comprehend. It is more like Parkinson's disease, where the immobility is quite clearly independent of the way the person wants to move. But it is also clearly linked to seriously abnormal mental state that none of us can imagine. When my wife was psychotic she did not have Catatonia but she did have involuntary movements that were similarly incomprehensible.

I cannot see any analogy with ME being useful.
 
Last edited:
This symptom of ME should be better known as it is devastating. Tom Kindlon shared the story of an Irish patient who had a terrible time in hospital because of it and which described my biggest fear.

With my ME, I do not get fatigue as such, I just stop, mid sentence, mid movement, a second or so later I can go again or maybe a few minutes if I am bad. The more effort I am expending, the longer I freeze.

However, If I have had a prolonged over exertion I freeze for longer depending on how bad I am and how much effort. On one occasion, I was at my grandson's birthday party. I let the noise and movement wash over me but it got too much and I could not move at all for about half an hour.

But no one noticed. Even my close family can't tell when it is happening and I can't tell them. They think I am asleep but I am panicking stuck inside my body. I have thought it is similar to locked in syndrome as the brainstem was spoken of as damaged in the days before CFS. After a while, I can force out a word or so if anyone is near to hear. Gradually it passes only leaving the cramp caused by being in an uncomfortable position.

The patient in the hospital (sorry I have forgotten the name but not her) did not get medication and tried to ask for help to the toilet but was left to wet the bed. And no food because the tray was brought and then picked up untouched.

The strange neurological symptoms we get have been forgotten since CFS and we now we have the spectre of FND held over us.
 
In Michael VanElzakkers Harvard talk he presented changes in Glutamate and Glutamine levels in the brain with PEM/changes in symptoms. Note : Very low number of patients.

In Karl Mortens NZ presentation he showed a 6 fold increase in Glutamate and a reduction in Glutamine in the blood.

Glutamate in the brain is thought to be involved in Catatonia.

Relevant slides of talks posted here
https://www.s4me.info/threads/quest...ith-dr-michael-vanelzakker.11496/#post-204728
 
Sly Saint said:
another similar condition 'encephalitis lethargica'
see thread here:
https://www.s4me.info/threads/encephalitis-lethargica-the-forgotten-epidemic.15829/
Click to expand...

Exactly, and over a million people supposedly got encephalitis lethargica after the Spanish flu in 1918 (an H1N1 type virus), with Parkinson’s like symptoms, psychosis, catatonia, etc.

I don’t think we can say for certain that there are definitely no possibly helpful pathophysiological similarities between these conditions and ME.
 
Last edited:
Jonathan Edwards said:
Yes but everything happening in the brain involves glutamate.
It's a bit like saying the food must be Italian because it includes tomatoes.
Click to expand...

Catatonia supposedly originates from disturbances in GABA, glutamate, and dopamine signaling. I know, it’s not really precise but just stating it doesn’t only involve glutamate.
 
Speaking about funny neurological symptoms, what is it when for a very brief moment (the duration of the blink of an eye), I feel like my brain is distracted and very busy with something, and then there is the sensation that something about the outside world is different even though everything looks exactly the same as before. Sometimes there is also a high pitched sound like in tinnitus that starts at low volume and then fades to nothing over a second or two. Is this some kind of mini seizure?
 
wigglethemouse said:
In Michael VanElzakkers Harvard talk he presented changes in Glutamate and Glutamine levels in the brain with PEM/changes in symptoms. Note : Very low number of patients.

In Karl Mortens NZ presentation he showed a 6 fold increase in Glutamate and a reduction in Glutamine in the blood.

Glutamate in the brain is thought to be involved in Catatonia.

Relevant slides of talks posted here
https://www.s4me.info/threads/quest...ith-dr-michael-vanelzakker.11496/#post-204728
Click to expand...

If you Google something like "glutamate MRI + Myalgic" then you'll see a bunch of studies. However, I wonder if they had adequate controls - or even how you would obtain adequate controls --- inactivity ---.

Karl's results sound interesting; however, I guess that the Glutamate/Glutamine ratio in the blood isn't a biomarker?
 
FMMM1 said:
Karl's results sound interesting; however, I guess that the Glutamate/Glutamine ratio in the blood isn't a biomarker?
Click to expand...
[Rant]
The frustrating thing is, there is no funding for Karl. He with his collaborators have the capability to measure 30,000 metabolites in multiple cohorts. He identified "VIP" markers but needs to replicate and try to discover what they are. If we are going on a fishing excursion shouldn't this be an area that gets funding.

While I'm on a rant he identified phenylalanine as an important metabolite. As has Chris Armstrong. High levels of phenylalanine can be toxic. Shouldn't we be looking at the phenylalanine pathway to dig deeper into what is happening. We can't because Karl Mortens interesting findings have no funding for further work and for replication of the work he has done. And we don't know if Glutamate is important unless he can replicate in different cohorts to make sure it is not an anomoly of the collection/preparation process. I just don't understand why the UK has not funded his work when it did fund another fishing project - GWAS. The purpose is the same - look at a large number of things in a large population and see what shakes out.

What I'm saying is we are left to speculate. Such as the purpose of this thread.
[/Rant]
 
You must log in or register to reply here.
Back
Top Bottom