Review Understanding Functional Neurological Disorder: Recent Insights and Diagnostic Challenges, 2024, Mavroudis et al.

Understanding Functional Neurological Disorder: Recent Insights and Diagnostic Challenges
Mavroudis, Ioannis; Kazis, Dimitrios; Kamal, Fatima Zahra; Gurzu, Irina-Luciana; Ciobica, Alin; Pădurariu, Manuela; Novac, Bogdan; Iordache, Alin

Functional neurological disorder (FND), formerly called conversion disorder, is a condition characterized by neurological symptoms that lack an identifiable organic purpose. These signs, which can consist of motor, sensory, or cognitive disturbances, are not deliberately produced and often vary in severity. Its diagnosis is predicated on clinical evaluation and the exclusion of other medical or psychiatric situations. Its treatment typically involves a multidisciplinary technique addressing each of the neurological symptoms and underlying psychological factors via a mixture of medical management, psychotherapy, and supportive interventions.

Recent advances in neuroimaging and a deeper exploration of its epidemiology, pathophysiology, and clinical presentation have shed new light on this disorder.

This paper synthesizes the current knowledge on FND, focusing on its epidemiology and underlying mechanisms, neuroimaging insights, and the differentiation of FND from feigning or malingering. This review highlights the phenotypic heterogeneity of FND and the diagnostic challenges it presents. It also discusses the significant role of neuroimaging in unraveling the complex neural underpinnings of FND and its potential in predicting treatment response.

This paper underscores the importance of a nuanced understanding of FND in informing clinical practice and guiding future research. With advancements in neuroimaging techniques and growing recognition of the disorder’s multifaceted nature, the paper suggests a promising trajectory toward more effective, personalized treatment strategies and a better overall understanding of the disorder.

Link | PDF (International Journal of Molecular Sciences) [Open Access]

 

A "good" review article. @dave30th FYI overview.

And for pwFND who wonder why we have a clear interest in this condition —

 

It never ceases to amaze seeing a powerful modern pseudoscience so late in technological development. And scrambling to explain how every assumption they made turned out to be wrong, all they can think of at this point is to take the consequences of illnesses they don't understand and reattribute them as their cause, the future affecting the past because reasons. It has the same troubling effect as a large astrology department at NASA would. Something unthinkable, because space sciences are serious business where outcomes always matter.

And showing just how thoroughly confused medicine as a whole is over symptoms, what they cannot explain because it's not simple enough to be put into a diagram. Hell, it's even more complex than metabolic cycles and they can handle those. What they can't handle is the limits of their knowledge. That there is a limit to it, one that shouldn't allow them to invoke magical explanations. And yet they sure do.

That's a bit funny:

They are not magically produced either. Or spiritually. Or cosmically. Or linearly. Or electronically. Or whatever. But of course the underlying belief system has always been grounded in the belief over feigning that they're still hooked to it. As if it even makes sense to speak of deliberately producing symptoms, when the only thing that may make sense would be to falsely report so, but even then it makes little sense anyway.

It's truly a modern version of "there be dragons" on maps. There is no such thing, but generations of being convinced of it are very hard to root out of a culture that is immune to factors outside itself and is protected by a self-defeating power imbalance that encourages hubris and, ultimately, failure.

I can never not think of this Simpsons joke when I read the nonsense these people put out. Just zero effort put into their work, the very picture of a lazy student who did their homework on the way to class.

 

There's also this that bothers me, the navel-gazing:

As if health care is the only work environment like this. But of course it is their work environment, and so the only one they can think of that is like this. Just pure uncut freebased hubris.

 

Yes. Perhaps this might be more accurately worded as "FND is estimated to be the diagnosis given in 5-10% of new neurological consultations, ranking it as the second most common diagnosis after primary (chronic daily) headache."

 

Some of the intro text reads like it's literally swiped from papers from the UK and US experts. And the second-most-common claims is of course complete bullshit. That's the lie perpetrated by the FND lobby based on misinterpreting a 2010 study, which found 5.5% were diagnosed with conversion disorder-type symptoms. They tripled the prevalence by adding in another whole group with "psychological" diagnoses. And conversion disorder diagnoses are themselves hard to believe. This claim that it's a common and prevalent condition is based only on their lumping together everyone whose symptoms do not have an identifable cauae.

 

I'm currently looking up the range of papers that got listed after the sterilisation suggestion (it alarmed me so much - and made me think of it being like when lots of people with ME got diagnosed with depression first it got claimed by some that indicated that was a common comorbidity rather than indicative of culture and misdiagnosis ie were people sterilising people as 'a fix' back in the day).

I'm quite surprised that of this list quite a few are papers of things like people with Parkinsons and Lewy body dementia.

But I'm already shocked and I've only got to the first paper in this list of 7 9 papers here: "Medical and surgical comorbidities present a clearer pattern in FND. Higher rates of surgical procedures and a history of neurological and other disease diagnoses have been recognized as important risk factors. The high rate of sterilization, particularly compared to gender-matched controls, might suggest a greater willingness to undergo surgical procedures in FND patients [34,50,51,52,53,54,55,56,57]. "

This first one is from 1997 (!) and is from a London Neuro dept: Slater revisited: 6 year follow up study of patients with medically unexplained motor symptoms | The BMJ

The authors include Anthony David, although he isn't the lead author (Crimlisk et al)

The abstract 'conclusion' was as follows: "Unlike Slater's study of 1965, a low incidence of physical or psychiatric diagnoses which explained these patients' symptoms or disability was found. However, a high level of psychiatric comorbidity existed."

and the key messages in the abstract:

But in the full article, In the results section it is noted that 31 of their sample had a history of organic neurological disorder: 15 with organic brain disease (inc migraine, epilepsy, parkinsons) and 16 with 'neurological diorder no brain disease' (inc 9 having previous disc surgery, 3 Peripheral nerve palsy, and then things like chiari malformation, myasthenia graivs, diabetic neuropathy). "The current unexplained symptoms were similar to those related to the previous neurological disorder in only 11 subjects (15%)."

It seems 3 of the 64 over the follow-up period were found to have alternative neuro diagnoses: myotonic dystrophy 4 years later, spinocerebellar degeneration 3 years after his admission (English not being his first language was the 'communication issue'), and paroxysmal hemidystonia. Two of these ended up with breathing and swallowing issues etc so pretty severe stuff and I don't know if those conditions these days would be any less likely to be misdiagnosed into FND or such deterioration could be prevented in the eventually diagnosed condition by earlier treatment?

This is from the discussion

Hmm mitigating factors for where they didn't pick up another neurological diagnosis - if communication problems may have played a part in two of these, wouldn't it be relevant to flag 'the issue of communication problems' rather than just list it as a mitigating factor, it seems a bit insightful of attitude?

5 subjects died by the time of follow-up but they didn't reflect missed neuro diagnoses. Is that good enough? and more importantly did their FND diagnosis or management play a part in anything missed or whether their death had been avoidable?

This, in 1997, explicitly notes that even if the diagnosis was correct it doesn't 'protect' people from developing serious physical illness. SO how have we got to the point now where it can mean people aren't being investigated?

The changed marital status and then concluding it must be 'reflecting a favourable change in personal circumstances' seems gobsmacking of the level of scientific thinking - cart before horse much? It is pretty tricky to complete a divorce (and all the other complications) if you are getting more and more ill, and I imagine that unless you are already in a very long-term relationship then going from dating to marriage becomes harder the iller you are?

they've associated comorbid psychiatric disorder with good outcome so hence suggested where that is present to treat those aggressively. Whereas almost leading on as a non-sequitur they've then said 'while for those with several physical symptoms and personality disorder' (I'm hoping they didn't mean it to read as it does) 'prevention of iatrogenic damage - what are they hinting at with that? - and 'cost effective management strategies aimed at damage limitation' doesn't sound particularly great? I'd like to know more about what they mean by 'damage limitation' and these strategies are?

This is the bit that is interesting:

 

and the second reference from this batch seems to be to me another 'funny little one' that could indicate a divisive agenda, and includes Stone, Carson and Sharpe on its list of authors: Which neurological diseases are most likely to be associated with "symptoms unexplained by organic disease" - PubMed (nih.gov)

This is the abstract (my bolding):

So the entire aim of this study was for those who had a neurological disease to be investigated where their symptoms were considered 'to be in excess of what would be expected'?

I don't know much about neurology, but couldn't that also be something that could also have been approached by people who were specialists in each disease and used to 'inform the spectrum' too - are these really 'unexplained' or just poor souls who had a really bad time of it

So they were already back in 2012 looking at people with already diagnosed organic diseases to add on diagnoses of 'unexplained' to them?

 

I couldn't help but notice that when looking at the abstract for this in the Journal of Neurology (couldn't find a full text) the following paper from 2019 was one of the ones highlighted underneath it as 'articles others are also reading':

The misdiagnosis of functional disorders as other neurological conditions | Journal of Neurology (springer.com)

also by Walzl, Carson, Stone

from the abstract:

Seems quite an agenda ie something that from that 2012 paper has continued into this paper in 2019 looking specifically at those who already have diagnoses of organic neurological disorders. ..

I'll note the conclusion (my bolding):

Given the paper I've seen in the past saying things like diagnosing FND in someone who ended up having CJD was 'essential' did they mean to actually write 'misdiagnosis can harm patients in either direction'?

Because I think given the authors it is worth someone saving this as evidence of their acknowledgement here?

 

OK so reference 51 (from the list after the sterilisation being more common line) is: Cohort study on somatoform disorders in Parkinson disease and dementia with Lewy bodies | Neurology

in its abstract the conclusion is:

the methods (so you have a sense of what the research was, and who/which conditions) are:

So how did this paper demonstrate or underline/back up the second line of the following (for which it is listed as a reference inferring), or even the first for the article at the top of this thread?

I have only got 3 papers in but not found one that talks of greater willingness to undergo surgical procedures or mention of sterilisation

am I missing something or are references supposed to actually back up what they are listed against in a paper?

 

reference 52 is a doozy that I can't see how it relates either, can't see mention of surgery or liking it or any sterilisation.

but has helped me to put a note on a few articles where the PHQ 15 was used as a measure of 'unexplained symptoms' (as this includes the usual suspects and concludes that these surveys are 'no better than chance' at identifying this, I thought that worth while).


The paper which includes Sharpe, Stone, Carson saying that the PHQ 15 doesn't identify people with unexplained symptoms better than chance I thought I'd do a quick google in case there were papers for which this reference might be relevant:

Somatic symptom count scores do not identify patients with symptoms unexplained by disease: a prospective cohort study of neurology outpatients - PubMed (nih.gov)

full text: untitled (researchgate.net)

abstract:

"Abstract
Objective: Somatic symptoms unexplained by disease are common in all medical settings. The process of identifying such patients requires a clinical assessment often supported by clinical tests. Such assessments are time-consuming and expensive. Consequently the observation that such patients tend to report a greater number of symptom has led to the use of self-rated somatic symptom counts as a simpler and cheaper diagnostic aid and proxy measure for epidemiological surveys. However, despite their increasing popularity there is little evidence to support their validity.

Methods: We tested the score on a commonly used self-rated symptom questionnaire- the Patient Health Questionnaire (PHQ 15) (plus enhanced iterations including an additional 10 items on specific neurological symptoms and an additional 5 items on mental state) for diagnostic sensitivity and specificity against a medical assessment (with 18 months follow-up) in a prospective cohort study of 3781 newly attending patients at neurology clinics in Scotland, UK.

Results: We found 1144/3781 new outpatients had symptoms that were unexplained by disease. The patients with symptoms unexplained by disease reported higher symptoms count scores (PHQ 15: 5.6 (95% CI 5.4 to 5.8) vs 4.2 (4.1 to 4.4) p<0.0001). However, the PHQ15 performed little better than chance in its ability to identify patients with symptoms unexplained by disease. The findings with the enhanced scales were similar.

Conclusions: Self-rated symptom count scores should not be used to identify patients with symptoms unexplained by disease."

 

reference 53 : Medical comorbidities in patients with psychogenic nonepileptic spells (PNES) referred for video-EEG monitoring - Epilepsy & Behavior (epilepsybehavior.com)

NB: no mention of surgery here, or liking it, or sterilisation.

I feel that they could have thought harder on the unfortunate acronym they have lumbered these patients with for a start. Not to be rude but given some things I've seen and the connection to at least sexism if not misogyny, and highlighting out female patients I think I'm right to be suspicious and note why on earth noone else has suggested it be an inappropriate 'stamp' to put on a patient set? Particularly given what they seem to be encouraging as demographics or claiming as likely history to 'watch out for'.

And is 'spells' even either the medical or commonly used term anyway that alternatives aren't more commonly used for?

This is from 2013 and worth reading through in case it is something unhelpfully misleading/influencing things that might be currently going on with some patients who are getting seizures - I don't know how influential this sort of thing is.

I've copied the shortened abstract, because I'm often suspicious of an ''epidemiologically-focused'' starter in an abstract that basically isn't really that, just a way to earmark out certain demographics or other conditions for 'consideration of this alternative diagnosis being more likely':

"Highlights

• Patients with PNES are more likely to have fibromyalgia, chronic pain, and IBS.
• Patients with PNES are more likely to have migraines, asthma, and GERD.
• Having at least of one these disorders is sensitive and specific for PNES.

Abstract
Differentiating between psychogenic nonepileptic spells (PNES) and epileptic seizures without video-EEG monitoring is difficult. The presence of specific medical comorbidities may discriminate the two, helping physicians suspect PNES over epilepsy earlier. A retrospective analysis comparing the medical comorbidities of patients with PNES with those of patients with epilepsy was performed in 280 patients diagnosed with either PNES (N = 158, 74.7% females) or epilepsy (N = 122, 46.7% females) in the Epilepsy Monitoring Unit (EMU) of the University of Pittsburgh Medical Center over a two-year period.

Patients with PNES, compared to those with epilepsy, were mostly female, significantly more likely to have a history of abuse, had more functional somatic syndromes (fibromyalgia, chronic fatigue syndrome, chronic pain syndrome, tension headaches, and irritable bowel syndrome), and had more medical illnesses that are chronic with intermittent attacks (migraines, asthma, and GERD). The presence of at least of one these disorders may lead physicians to suspect PNES over epilepsy and expedite appropriate referral for video-EEG monitoring for diagnosis."

 

Also a bit worrying that this one is from 2013 and notes it is difficult to discriminate these, yet there is a paper linked to from it that suggests the opposite (so people picking up said diagnosis then might have the impression it is 'foolproof') - which is it?: The problem of psychogenic symptoms: is the psychiatric community in denial? - Epilepsy & Behavior (epilepsybehavior.com)

Abstract
Psychogenic symptoms are common and pose an uncomfortable challenge. Among psychogenic symptoms, psychogenic nonepileptic seizures (PNES) are common and have been extensively studied. They are unique in that, unlike most other psychogenic symptoms, they can be diagnosed with near certainty. PNES can be used as a model, as almost everything that applies to PNES applies to other psychogenic symptoms. According to DSM-IV, somatic symptoms are the main manifestation of three groups of disorders: somatoform disorders, factitious disorder, and malingering. Treatment is challenging. Unfortunately, psychogenic symptoms tend to be neglected. For example, the American Psychiatric Association has abundant written patient education material available on diverse topics, but none on somatoform disorders. Psychogenic symptoms are also not the subject of much clinical research. A search of the journal Neurology for 1994–2003 for the word psychogenic in the title found 21 articles, only 4 of which on topics other than psychogenic seizures. A similar search for original articles in the New England Journal of Medicine found no articles with psychogenic in the title and two with psychogenic in the abstract. Thus, there seems to be a severe disconnect between the frequency of the problem and the amount of attention devoted to it.

 

Reference 54: CRPS_FND_manuscript_150818.pdf (dundee.ac.uk)

Maybe this is the one that mentions 'surgery' because they do say in their introduction: "Complex regional pain syndrome (CRPS) is a disabling chronic pain condition that may follow physical injury to a limb, either through surgery or trauma."

Popkirov et al (2019) includes both Carson and Stone

Well it seems the Popkirov paper includes the following in its full text:

BUT HOw do these claims about Complex Regional Pain Syndrome marry up with the findings of a genetic cause for it on the following thread: Evidence of a genetic background predisposing to complex regional pain syndrome type 1, 2023, Shaikh et al | Science for ME (s4me.info)

"Conclusion
A single SNP in each of the genes ANO10, P2RX7, PRKAG1 and SLC12A9 was associated with developing chronic CRPS-1, with more males than females expressing these rare alleles. Our work suggests the possibility that a permissive genetic background is an important factor in the development of CRPS-1."


So why is this 2024 paper including this Popkirov paper on CRPS and NOT the Shaikh et al (2023) paper?

I know why, because they've read the 'FND' and anything that backs it up stuff, but not the latest updates on any of these conditions that makes the papers and suggested links questionable?

 

Reference 55 relates to Cauda Equina Syndrome - in particular scan-negative vs scan-positive (MRI):
The clinical features and outcome of scan-negative and scan-positive cases in suspected cauda equina syndrome: a retrospective study of 276 patients | Journal of Neurology (springer.com)

It again includes in its authors Stone and Carson and is from 2018 (Hoeritzauer et al, 2018)

The conclusion is as follows:

As this one is beyond my knowledge but there may be those who are more able to look into this one and understand it and see through any issues I'm keeping this short.

I note that perhaps this one might relate to the sentence it actually references re: surgery being more common, but I don't think so given the context is just follow-up on those who present with CES and get a scan that is either positive or negative and are followed up 16months later.

 

I've taken a pause before looking properly at the last two papers. But, as you've mentioned it, one is on headache and the other migraine (Migraine associated with conversion disorder (Babinski's migraine). Analysis of a series of 43 cases - ScienceDirect )

The headache one: Functional/Psychogenic Neurological Symptoms and Headache (rwevansmd.com)
has a big old spiel bit about whether it is functional and the reasons why physicians mightn't be keen on seeing their headache patients that way

"What If Functional Neurological Symptoms Were Considered As Legitimate As Migraine?—For both these cases, the problem may lie in the fact that many neurologists have difficulty taking seriously or believing patients with functional weakness and dissociative attacks. There is still widespread support among neurologists for the idea that deception is playing a part in these symptoms even if they do not think it is the whole story.10 Certainly, 64% of the respondents of our survey agreed that these patients often deliberately exaggerate their symptoms (see Appendix I). This may be in large part because of the way that functional motor symptoms in particular can be shown at the bedside to be inconsistent (whereas there is no similar test for headache). No wonder, then, that headache specialists do not want “honest” headache patients to be associated with “dishonest” functional/psychogenic patients. Only 9% of headache specialists thought that patients with headaches exaggerate. But imagine how much more interesting the debate would be, if both types of symptoms could be taken equally seriously. In that scenario we could ask much more interesting questions not only about the biology of functional neurological symptoms but about the psychology of headache."

 

I'm getting quite disturbed going through this. Appreciate anyone else who wants to pick away at this too, as there is a certain amount of short bursts needed because of how shocking it is when I realise how many areas they have 'gone at' over the years to create some add-on. Some of these are pretty chilling when you think about the ambition / agenda behind it?

I'm also coming to the realisation that whilst it is a whole new territory to cover meaning expansive work it really isn't 'different territory' because of what its aims are - creating territory from it seems looking into already known organic diseases and seeking to find or claim 'bits of that' or 'patients who have' functional chunks from those.


I agree on your point about status - then in relation to your first line there is the question about 'consent' (and therefore ethics) if something turns out to be retrospective and maybe the individual was unaware they were being investigated for such etc. So much of the stuff in this particular area seems to be retrospectives from potentially selective samples that it almost when reading one after the other kids you into thinking this is some sort of methodological OK or norm.

I think what I have spotted (when you compare eg the 1997 one which appears to be a lauded neurology centre but notes it has a 'different demographic' to normally found ie less 'lowly/vulnerable' patients perhaps but more 'status' in the staff themselves?) is that it seems to be more about power-differential

SO status but at its heart vulnerability of patients, and there certainly seem to be common themes in which clinics are being used as cohorts because the researchers 'have access' are then being perhaps used to define the epidemiology?

I can't help but notice that most of these papers I have looked at are from the UK (one is Spanish?) so reliant on the pretty strange vs world norms set-up of the NHS

and how there aren't US references for example.

And how access to healthcare is pretty different there. As would be the power differential in the interaction potentially

Of course the first and second authors listed for this paper appear to be from Leeds, UK but then there are countries like Greece, Morocco and Romania

there are 173 references listed (although I can already note from the small selection there appear to be common names in quite a few of these, so I don't know how few actual cohorts this covers - it might be very small indeed by comparison if it is mainly from a few clinics/areas doing a lot of papers) so going through to see how representative this is of the international perspective isn't a small task.