Abnormal cerebrospinal fluid cytology in functional movement disorders, 2024, Serranová et al

Abstract

Objective
The role of inflammation and neuroimmune mechanisms, which have been documented in various neuropsychiatric disorders including the seizure subtype of functional neurological disorder, remains unclear in functional movement disorders (FMD). To explore these mechanisms, we analyzed selected inflammatory markers in cerebrospinal fluid (CSF) in patients with FMD.

Methods
We compared CSF markers in 26 patients with clinically established FMD (20 females; mean (SD) age 43.3 (10.9); disease duration 3.9 (3); range 0.1-11 years; mean follow-up after lumbar puncture 4.3 (2) years, range 0.5-7 years) and 26 sex and age-matched clinical controls with non-inflammatory non-neurodegenerative neurological disorders, mostly sleep disorders.

Results
65% of FMD patients vs. 15% of controls showed cytological abnormalities (i.e., increased white blood cells (WBC) count, signs of WBC activation, or both (odds ratio (OR) = 9.85, 95% confidence interval [2.37, 52.00], p < 0.01, corrected), with a significantly higher frequency of an isolated lymphocytic activation 35% vs. 0% (OR = ∞, 95% confidence interval [2.53, ∞], p < 0.05, corrected). There were no differences in CSF protein and albumin levels, quotient albumin, IgG index, and oligoclonal bands. CSF abnormalities were not associated with more severe motor symptoms or a higher frequency of depression in FMD.

Conclusions
Our results suggest a possible involvement of immune mechanisms in the pathophysiology of (at least a subtype of) FMD that deserves further investigation.

Paywall, https://journals.lww.com/psychosoma...rmal_cerebrospinal_fluid_cytology_in.211.aspx

 

What good timing. This is exactly the kind of research we need to dismantle the FND bandwagon.

 

Yet it probably won't. The FND researchers will just point at this sort of research, proclaiming 'See, FND is actually a thing, these results prove it!', despite years of advocating for the smallest amount of investigation that can be got away with.

 

Yes the hypocrisy is infuriating. It really is a lose-lose situation for everyone but the FND advocates.

However, the only way out of this mess is through research and even small steps are a win to me. If we can demonstrate specific abnormalities in FND patients then at least there tangible biological processes that can focused on and not some vague software issue. Maybe its wishful thinking, but we have to start somewhere even if research efforts have been sabotaged by these folks for decades.

 

These patients had 'mostly sleep disorders'. Goodness knows whether anyone outside the Czech Republic would diagnose them as FND.

And if there were no differences in CSF protein levels it is a bit difficult to know what to make of cell population differences. And who were the 'clinical controls'. Maybe people with normal CSF values?

They may have found some interesting subtle cell changes in people with sleep disorders but I would not put too much weight on the relevance to FND

In a way they fall for the logical contradiction:

We studies people with neurological problems and no abnormalities.
We found abnormalities.
So people with neurological problems and no abnormalities have abnormalities.
Er?

It is an old trick.

 

It's kinda like me saying "I never got sick ever since I got sick", mostly for the humor. In case you are serious though, the contradiction could be resolved by inserting "known" and "previously unknown" in front of "abnormalities".

No idea about the specifics of the paper, but I personally find it rather interesting that they are finding physical basis for what they thought was functional, same way they are finding physiological basis for psychiatric problems.

 

No, you can't get away with that.
They said that these people were known to have FND. It had been proved that they had an illness with abnormalities. Or at least they were recruited on the basis that this was certain.

They should have recruited people on the basis of some other definition - which might have been a load of people who couldn't sleep, in practice.

I came across this trick with my first clinical paper. It was a study of the 'Benign Hypermobility Syndrome' which was defined as hypermobility without any internal organ involvement. We looked at heart valves and the paper said (wrongly) that our patients had more heart valve problems. In other words they could not be classified as Benign Hypermobility Syndrome after all. The error was to assume something was true and then try to show it wasn't. The project director never seemed to realise how barmy that was.

 

So, you are saying that the subjects in this study did not have FND to begin with, because they are found to have physiological abnormalities? Would you say the same thing if they ever find physiological basis for ME/CFS as well? ME/CFS has similar diagnosis of exclusion, after all.

I can understand though, the analogy could be something like recruiting IIH patients for ME/CFS and then declaring that they found the cause of ME/CFS to be intracranial pressure.

 

Correct. And that underlines the conflation we constantly make between mechanistic disease concepts, syndromal disease concepts and 'disease' disease concepts - the latter being some sort of intuition that there is some mysterious identity that is 'a disease'. When it comes to picking apart how these things work it is essential to de-conflate all the things. A term like rheumatoid arthritis stands for both a cause and an effect so if you are trying to see how cause relates to effect you have to undo this terminology. Natural language does this sort of conflation all the time. Physicists do it all the time with terms like 'action', 'wave' and 'coherence'.

ME/CFS is a syndrome term that is often co-opted as a mechanism or disease term but, whichever, does not entail 'no abnormalities found'. It just entails that no abnormalities that are explained by other known disease concepts and are known to produce similar symptoms can account for the clinical presentation.

 

Not sure how you can make that distinction between ME/CFS and FND unless you are saying that FND is a well-defined disease by its cause, effect (and treatment). Both describe symptoms only and both requires "unexplained by other conditions" as far as I know.

 

But it is more subtle. 'Conditions' brings in the conflation again.

ME/CFS is a clinical picture not explained by processes known to cause other identifiable clinical syndromes. It cannot be due to focal demyelination or depletion of dopaminergic neurons of the sort responsible for MS or Parkinson's.

FND is a clinical picture in which no causal processes of any sort can be found on investigation. The exclusion is supposed to be structural but in practice it includes haematologic or biochemical processes like hypothyroidism. And the absence of identifiable process is the defining concept. It isn't for ME/CFS. In ME/CFS it just happens to be true for now.

Very often in medicine the same patient can be classified three or more different ways depending on whether you are classifying by process or clinical picture or 'disease'. They may have respiratory insufficiency. They may also have tuberculosis. They may also not have mycobacterial infection because it has been successfully eradicated. Statements about patients under one category may not apply to another. An awful lot of the heated debate about diagnostic labels arises from the intuition that these are 'separate diseases'. In practical medicine that is problematic.

 

So, that absence of an identifiable process is true for FND, but not for ME/CFS even though it appears so, because... it will be eventually identified for ME/CFS? That sounds like an awful lot of a priori to me. What basis do you have for that faith?

 

I thought we agreed that FND is a label to describe a condition where some symptoms can not be currently be attributed to some identifiable process. If FND excludes any biochemical process in perpetuity, then it can not exist by definition. How can something within the universe happen without a cause? I find this confusing as I think you agree that the absence of identifiable process in FND only happens to be true for now. Do you really think there are people who should be labeled as having a condition in which it is impossible to find the underlying process.

Also, how could you ever run a study looking at people with FND if you assume that it is indeed impossible for there to be any identifiable pathology? This is exactly what I meant when I said that the FND label slows research progress. If you assume that nothing will ever be found, you won't look and you won't find anything. I think this can be a very harmful and dangerous mindset to have.

 

This is the crux of it. You can't.
The point is that FND is NOT a disease category. It is a category that someone can fall under at one time and not at another.

This particular example is unconvincing but in the case of our study of 'Benign Hypermobility Syndrome defined as having no internal organ features' once we had found internal organ features the patents clearly no longer fell under this category.

So the authors' claim of 'clinically established FMD' actually is them failing to understand that you can never 'establish' FMD. The patients may fit that category as far as one can see, that's all. And if the CSF findings are relevant then these people do not have FMD any more.

I am actually quite intrigued as to how people with sleep disorders get diagnosed as having a movement disorder. Maybe they suffer from restless legs syndrome, which to my mind is better described as restless legs syndrome than FMD because it has a plausible link to physiological changes on going to bed and is itself a well recognised category.

 

Uh oh! Any corrections or clarifications made???

 

Who knows? But the penultimate author is Espay, a well-known and widely published FND expert at University of Cincinatti. Presumably he didn't have issues with the identification of the patients in the study as having FND. Doesn't mean it was all fine, but it does suggest that diagnosing them as such wasn't a stretch from the current perspective of the FND specialists.

 

But that's a bit like saying that a famous misogynist thinks all women are stupid so we can accept a paper with his name on as describing uniformly stupid women!

Although clearly you are right that one person outside the Czech Republic thinks they have 'FMD'. But that might only be for the purposes of another tick on their publication list.

 

Ahh ok I understand the nuance now. People with FND do not have any pathology but only in a definitional sense. It is impossible to have FND and also have some pathology. Of course, there is some unknown pathology so the label is only useful in acting as a waiting zone. Once we have a better label, then the patient no longer has FND and will get a more useful name. Assuming the FND label does not change, then some day it will no longer exist. Do you have any idea why FND was defined in this way and not as "an unknown issue"? This might have avoided the possible implication that no such biological FND pathology exists.

You could also still run an 'FND' study in order to try and reclassify patients. If this study was accurate and more broadly applicable, then 65% of FMD patients would no longer technically have the condition as you say.

 

It must also be the case that almost everyone is using the term incorrectly. Most of the websites I have visited suggest that FND is due to some brain mismatch or software issue. If this were the case then these people wouldn't have FND they'd have some other issue.