The neuroimaging evidence of brain abnormalities in functional movement disorders, 2021, Sasikumar and Strafella

[Hutan]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418342/

Abstract
Neuroimaging has been pivotal in identifying and reframing our understanding of functional movement disorders. If accessible, it compensates for the limitations of the clinical exam and is especially useful where there is overlap of functional symptoms with classical presentations of disease. Imaging in functional movement disorders has increasingly identified structural and functional abnormalities that implicate hypoactivation of the cortical and subcortical motor pathways and increased modulation by the limbic system. Neurobiological theories suggest an impaired sense of agency, faulty top-down regulation of motor movement and abnormal emotional processing in these individuals.

This framework challenges our traditional understanding of functional movement disorders as distinct from the deceptive term of ‘organic’ diseases and proposes that these conditions are not considered as mutually exclusive. This update summarizes the literature to date and explores the role of imaging in the diagnosis of functional movement disorders and in detecting its underlying molecular network.

 

[Andy]

So when properly investigated physical abnormalities are found in people diagnosed with a functional condition, and somehow that supports the idea of functional conditions, rather than highlighting how flawed it is?

 

[Hutan]

As I mentioned elsewhere, papers like this are an interesting reflection of psychosomatic medicine proponents scrambling to reposition themselves as the evidence comes in for physical, medically treatable causes of various health conditions that have carried the 'functional' label.

FMDs can mimic a range of known movement disorders, including tremor, dystonia, myoclonus, gait disorders and parkinsonism.4However, these movements are often distractible and entrainable unlike in classical manifestations of disease.5 They can also accompany atypical behaviours like grimacing, sighing, extremely slow movements and whole-body movements with simple motor tasks.5

Functional disorders can either occur independently or accompany classical illness, which makes the distinction challenging with examination alone.6,7 Functional neuroimaging is a means to address this limitation and can further clarify the nature of complex clinical presentations. Increasing research in this field has revealed that functional neurological disorders are associated with distinctive imaging changes, which has further informed several theories about its underlying pathophysiology.8 In identifying the neurobiological models of FMDs, we begin to appreciate it as a new disease entity and identify potential avenues for treatment.

Functional disorders have been previously referenced as psychogenic, somatization or conversion disorder. These terms imply that the symptoms are derived from a psychological trigger, which is not a requirement to diagnose functional disorders.9 While terminology plays a key role in distinguishing from malingering or feigning symptoms, an accurate term has been challenging because of a limited understanding of the underlying physiology of functional disorders.4 Invoking a psychogenic cause in the absence of identifiable risk factors falsely labels individuals. Based on a study by Stone and colleagues,10 the term ‘functional’ was the most preferred by patients.

Here, the inference is that being labelled with a disorder that has a psychogenic cause is not a positive outcome for the patient. We see the terms 'psychogenic', 'somatisation' and 'conversion disorder' being replaced by 'functional disorder' not only because the patients like it, but because the house of cards doesn't fall down when the patients don't have a history of trauma, or obvious psychological issues. Or when pathologies, physical evidence of the disease, are identified. The term used can stay the same; the promoters of magic medicine can subtly shift and retain their 'expert' status.

When DAT-SPECT (using TRODAT-1) was used on five individuals with clinically established functional parkinsonism, two demonstrated a presynaptic dopaminergic deficit, attributing their presentation to an underlying neurodegenerative aetiology instead.11

This is talking about misdiagnosis, where two out of five people with 'clinically established functional parkinsonism' were found to have an 'underlying neurodegenerative etiology instead', a disease cause that can be treated.

Similarly, DAT-SPECT (using 123I-FP-CIT) revealed a neurodegenerative aetiology in two of three patients initially suspected to have functional parkinsonism.13

More mis-diagnosis.

In a study of nine individuals with suspected functional parkinsonism, further testing on the individual with bilateral decrease in 123I-FP-CIT striatal uptake further identified a parkin (PRKN) gene mutation.14

and more

Imaging can also establish the diagnosis of functional parkinsonism by demonstrating normal DAT density uptake.15 In a study of 33 inconclusive cases, 123I-FP-CIT SPECT identified nigrostriatal degeneration in nine patients

more

In a 66-year-old male with gait instability, left laterocollis, intermittent mutism and verbal perseveration attributed to a FMD, had an FDG-PET which showed hypometabolism in the occipital lobe suggestive of dementia with Lewy bodies instead.

more

Elmalı and colleagues19 describe a case of a 31-year-old female who presented with a postural and action tremor that was irregular and altered in direction, prompting the diagnosis of a functional tremor. However, MRI brain revealed abnormal thalamic and pontine signal changes suggestive of an alternative pathology. A family history of cirrhosis prompted the workup for Wilson’s disease, with which she was subsequently diagnosed.19

and more

Similarly, a 20-year-old male with a variable, distractible rest and postural tremor in the arms had a spine MRI that revealed atrophy at the C5-7 level with anterior displacement of the dura with neck flexion. This was suggestive of Hirayama disease and with surgical intervention, his tremor improved up to 3-months follow-up.20

Here the patient had a tremor that varied with distraction - a key test for functional movement disorders according to Jon Stone (ref #5)

FMDs can mimic a range of known movement disorders, including tremor, dystonia, myoclonus, gait disorders and parkinsonism.4However, these movements are often distractible and entrainable unlike in classical manifestations of disease.5

Surgery on identified structural spinal atrophy improved the tremor.

But, despite all this evidence that new technology and clinician diligence can keep discovering non-psychogenic causes, there is still belief in the concept of movement symptoms that arise out of nothing. Read this next paragraph, for example:

Perhaps where imaging is most useful is in the diagnosis of FMDs that coexist with classical pathology.6,7This is particularly challenging because FMDs can demonstrate a good placebo response to intervention, likely due to involvement of the mesocorticolimbic pathways.3,6 When evaluating nine patients who were referred for suspected functional parkinsonism, 123I-FP-CIT SPECT confirmed diagnosis in three, and five patients had a combination of functional and degenerative parkinsonism. The remaining patient was attributed to the latter category based on clinical suspicion but had a normal SPECT scan. Long-term follow-up for an average of 2.3 years supported the diagnoses.21 In another study by Lang and colleagues,6F-DOPA PET in four individuals revealed diminished unilateral striatal uptake in one individual, suggesting an overlap with degenerative parkinsonism.

The paper tells us that functional movement disorders can coexist with actual pathology; and that a lack of identified pathology confirms a functional diagnosis. As we've mentioned elsewhere when reviewing papers that report finding actual pathology in patients as their diseases became more florid, there is a resolute clinging on to the functional diagnosis. A brain turning to mush over a matter of months is, the functional disease experts tell us, not a reason for a patient to not also have a functional disorder.

 

[Hutan]

Functional imaging studies demonstrate that individuals with FMDs have altered patterns of cerebral activation, thereby suggesting genuine pathology instead of feigned deficit.22-24 They demonstrate structural and functional differences from normal controls, particularly with the cortical and subcortical structures involved in the regulation of movement and emotion.24,25

There's some really nasty patient labelling going on here, where differences in brain activation that are poorly understood are so often bent to suit a 'not really sick but at the same time, sick' narrative.

Unilateral functional leg weakness was associated with reduced regional CBF and increased activation of the orbitofrontal and anterior cingulate cortices.34 These regions are implicated in emotional processing, especially in that of prior traumatic experiences.34 When exposed to fearful and happy faces, individuals with functional weakness demonstrate a lesser difference in the activation of the right amygdala compared to healthy controls. This suggests a tendency towards increased excitability and decreased habituation.33

One study pointed out a correlation between mental health impairment, increased anxiety and increased right amygdala volumes.44 The same group also described an inverse correlation between the degree of physical impairment in FMD and the volume of the left anterior insula on imaging.44 They also demonstrated that individuals with higher depersonalization scores have an increased thickness of the right lateral occipital cortex compared to healthy controls.45 Functional hemiparesis also correlated with increased thickness of the premotor cortex compared to healthy controls.46 However, the consistency of these structural changes are inconsistent in the literature.

We've seen the poorly done studies of brain imaging; it's no surprise that the findings are inconsistent. And yet, these flaws and inconsistencies are no barrier to FMD proponents speculating wildly on the psychological causes of motor impairments.

The heterogeneity of the studies, small sample sizes and poor reproducibility challenge our ability to make meaningful conclusions about the imaging changes currently described in the literature. Functional disorders can be associated with altered emotional processing and psychosocial stressors,50 which also limits the interpretation of the structural changes in the limbic system as we cannot link cause and effect.

We have yet to determine a unified mechanism to explain the phenomenon of FMDs. In addition to the aforementioned limitations, this is also perhaps because of variation in individual responses to stressors, which can further impact the biochemical basis in their condition. Moreover, the predilection and response to stress have a complex underpinning that includes genetic, epigenetic and social influences,50 which further challenges our interpretation of these findings. Nevertheless, the disrupted neurobiological network suggests the need to reconceptualize our understanding of functional disorders. In recognizing these abnormalities we can no longer distinguish them from the so called ‘organic’ movement disorders, thus rendering the term ‘organic’ misleading and deceptive.

I think this paragraph illustrates my point. These authors are all over the place. They are at once admirably trying to point out that new technology can find causes for motor disorders, causes with real treatments. But they still manage to be in 'God of the Gaps' mode at the same time. They are at once pointing out some of the flaws and inconsistencies of the brain imaging studies that supposedly provide evidence of FMD and emotional processing, while still promoting patient-blaming labelling.

Long-term follow-up of these patients can also identify whether the structural and functional imaging changes are reversible with interventions such as cognitive behavioural therapy and physiotherapy. The more we understand the neurobiological basis of FMDs, the more avenues can be targeted for therapeutic intervention.

And of course, the answer as always is CBT. Well, it will be, when more research is done.

This work was supported by Canadian Institutes of Health Research

 

[Hutan]

This paper is mentioned on other threads:
Functional Neurological Disorder (FND) - articles, social media and discussion
Extensive Brain Pathologic Alterations Detected with 7.0-T MR Spectroscopic Imaging Associated with Disability in Multiple Sclerosis, 2022, Heckova+

This thread has more examples of the phenomenon of having an extremely serious brain degenerative disease while supposedly also having a functional overlay. It includes a link to another thread with the case study of the woman I was referring to upthread with CJD:
Functional neurological symptoms as initial presentation of Creutzfeldt-Jakob disease: case series 2022 Gómez-Mayordomo et al

 

[SNT Gatchaman]

Functional disorders have been previously referenced as psychogenic, somatization or conversion disorder. These terms imply that the symptoms are derived from a psychological trigger, which is not a requirement to diagnose functional disorders. While terminology plays a key role in distinguishing from malingering or feigning symptoms, an accurate term has been challenging because of a limited understanding of the underlying physiology of functional disorders. Invoking a psychogenic cause in the absence of identifiable risk factors falsely labels individuals. Based on a study by Stone and colleagues, the term ‘functional’ was the most preferred by patients.

And yet we have What Does Neuroscience Tell Us About the Conversion Model of Functional Neurological Disorders? (2019)

(TLDR: it's totally conversion disorder you guys, don't worry about the name.)

As Hutan notes, the neuromancers have really managed to tie themselves into a Gordian knot. In this analogy, perhaps MRI will be Alexander's sword.

Alexander was challenged to untie the knot. Instead of untangling it laboriously as expected, he dramatically cut through it with his sword, thus exercising another form of mental genius. It is thus used as a metaphor for a seemingly intractable problem which is solved by exercising an unexpectedly direct, novel, rule-bending, decisive and simple approach to the problem that removes the perceived constraints.

 

[rvallee]

Neuroimaging has been pivotal in identifying and reframing our understanding of functional movement disorders

I am not aware of a single thing supporting this, other than ideologues saying this on a loop for years without any basis. What are they even talking about? Other than when something is found it's no longer "functional"/conversion disorder. Other than the relatively recent and egregious BS about "functional overlays", which is basically "heads I win, tails you lose".

And if nothing else, findings invalidate the entire premise since despite the Big Lie, the only relevant factor here is "none of our current tests tell us anything relating to some known pathologies and we've been doing things this way for over a century and cannot possibly stop with our credibility intact".

How in the hell do they somehow manage to cram through "agency" here?

 

[Sid]

As I mentioned elsewhere, papers like this are an interesting reflection of psychosomatic medicine proponents scrambling to reposition themselves as the evidence comes in for physical, medically treatable causes of various health conditions that have carried the 'functional' label.

We can expect to see quite a bit of this scrambling to reposition now that updated technologies like 7 tesla MRI scanners are becoming available. Any new diagnostic procedure in neurology puts a lot of psychobabble careers at risk.

 

[Sid]

This thread has more examples of the phenomenon of having an extremely serious brain degenerative disease will supposedly also having a functional overlay. It includes a link to another thread with the case study of the woman I was referring to upthread with CJD:
Functional neurological symptoms as initial presentation of Creutzfeldt-Jakob disease: case series 2022 Gómez-Mayordomo et al

This infamous study should send a chill down anyone’s spine. Despite clear evidence of organic disease and a fatal outcome, they still would not admit that they were wrong about FND. I hear this a lot anecdotally as well. Cases where someone was told they had FND, then a real diagnosis is made and the neurologist refuses to remove FND from the chart. Instead of mea culpa you get told you have both. “Functional overlay.”

 

[livinglighter]

I hear this a lot anecdotally as well. Cases where someone was told they had FND, then a real diagnosis is made and the neurologist refuses to remove FND from the chart. Instead of mea culpa you get told you have both. “Functional overlay.”

Many people are misdiagnosed so why can’t the same be the case for people with FND?

 

[Hutan]

It's a really good question.

Maybe it is because the FND doctors really do know that giving someone that diagnosis is making an unfavourable statement about that person's personality. And, if the cause of the symptoms does actually end up being a tumour, or MS, or Creutzfeldt-Jakob disease, then the FND doctor might feel bad about having made such an assumption about someone who was really sick. And the patient and their family might also feel highly aggrieved about that, there might even be thoughts of legal action against the doctors. The family might feel guilty for having jumped to the conclusion that their loved one was just not thinking the right thoughts, rather than having a physical disease.

So, maybe, the conclusion 'oh, they had a real disease but with a functional overlay' serves lots of purposes. The FND doctors get to feel okay about themselves and continue diagnosing people with FND, because they weren't wrong. The family also don't have to feel so guilty about not pushing for more tests in a timely way or not providing support. The patient and family are a whole lot less likely to take legal action alleging medical negligence, because they either believe the overlay idea, or they understand that any litigation is going to have family trauma and the patient's sanity interrogated.

 

[dave30th]

Another thing that seems contradictory about the whole thing is that every article on diagnosis/management says how challenging it can be to diagnose. At the same time, they claim the purported rule-in clinical signs (Hoover's sign, entrainment, etc) are highly specific. If a test or sign is highly specific, how can the entity also be hard to diagnose accurately?

 

[ToneAl]

Another thing that seems contradictory about the whole thing is that every article on diagnosis/management says how challenging it can be to diagnose. At the same time, they claim the purported rule-in clinical signs (Hoover's sign, entrainment, etc) are highly specific. If a test or sign is highly specific, how can the entity also be hard to diagnose accurately?

Because tests such as hoovers are circular and false positives exist

 

[Hubris]

The culture of disdain is very deeply rooted within medicine. I remember reading a literature review on autoimmune encephalitis, which is an illness with autoantibodies directly attacking your brain, where you can easily die within weeks if not treated. When I read that 30% of those patients have a negative MRI, I asked myself how the hell it is possible for neurologists to be so confident in knowing nothing is wrong with you when their diagnostic tools have such severe limitations. Surely, any rational person couldn't not have doubts about their judgement, especially considering the huge amount of harm it would do to the patient. Eventually, I learned that this way of thinking is the standard and nobody really cares that these patients are a playground for certain doctors to dish out abuse.

In this context, the mental gymnastics that are happening to justify the coexisting of FND and neurodegenerative illness as diagnostic tools improve are not that surprising.

 

[SNT Gatchaman]

every article on diagnosis/management says how challenging it can be to diagnose. At the same time, they claim the purported rule-in clinical signs (Hoover's sign, entrainment, etc) are highly specific. If a test or sign is highly specific, how can the entity also be hard to diagnose accurately?

How often does their literature indicate they are diagnosing FND/overlay without rule-in signs? Is it the case that they can no longer make the diagnosis without positive rule-in signs?

If those signs aren't actually present in many patients, but they still want to give them a diagnosis of FND, that would tend to make things challenging...

 

[livinglighter]

How often does their literature indicate they are diagnosing FND/overlay without rule-in signs? Is it the case that they can no longer make the diagnosis without positive rule-in signs?

If those signs aren't actually present in many patients, but they still want to give them a diagnosis of FND, that would tend to make things challenging...

I'm sure my ME diagnosis was referred to what is now called FND without rule-in signs - if that even makes sense.

I was told since I have ME, which is not neurological, it meant I have a non-organic illness. What happened to the lovely neuropsychological evaluations used at the time to decide if symptoms were simply organic or not?

Now it is roll out the neuro-psych tests on certain patients because now they can diagnose FND.

 

[Hutan]

How often does their literature indicate they are diagnosing FND/overlay without rule-in signs? Is it the case that they can no longer make the diagnosis without positive rule-in signs?

What rule-in signs? There's a paper discussed here on the forum that actually said that the bringing in of a soft toy to the clinic was a sign of FND (yes, really), along with the suggestion that being young and female contributed to the FND diagnosis.

Here it is:
Evidence-Based Practice for the Clinical Assessment of Psychogenic Nonepileptic Seizures, 2020, Baslet et al

Presence of a teddy bear brought into the EEG unit predicted PNES with 88% - 99% specificity and 5%-13% sensitivity (9, 10)

(Just in case you missed it, read the title of that paper again - 'evidence-based' and 2020)
If you have a teddy bear and you are in an EEG unit, you almost certainly have psychogenic seizures.

 

[livinglighter]

What rule-in signs? There's a paper discussed here on the forum that actually said that the bringing in of a soft toy to the clinic was a sign of FND (yes, really), along with the suggestion that being young and female contributed to the FND diagnosis.

Here it is:
Evidence-Based Practice for the Clinical Assessment of Psychogenic Nonepileptic Seizures, 2020, Baslet et al

I remember the toy one and chuckled to myself, thinking there is no way this BS will catch on and now look at where we are. The acceptance was abnormally rapid. One day FND was about toys, the next day it was in the first acquired brain injury & neuro conditions guideline. Which reminds me, how did it get in there without structural brain abnormalities being a feature of the illness at the time?

 

[rvallee]

I'm getting a bit lost about one thing: functional disorders vs FND. Is FND supposed to be some different thing from the general use of "functional disorders", which means the same thing, and under which all chronic illness has been classified by many?

Seems like there's recently been this creation of a separate but equal thing here, where ME, fibromyalgia, IBS, POTS and other stuff is considered generically "functional", meaning conversion disorder, meaning psychosomatic/stress/trauma/anxiety/whatever, but FND is the same thing, but they added this recent bit about a "rule in" sign, one that clearly doesn't matter anyway since if it's not there it's still "functional", and it means the same thing, has the same "definition", if one can call it that, and the exact same treatment approach.

Really seems like they're eating their cake and having it too here. Because the broader generic idea of "functional" remains the modern label for psychosomatic. And obviously FND is functional neurological disorder, so quite obviously the same as functional disorder. It's like it's all the same thing, but at the same time there's this big pretense of a separation that is, somehow, a subset, one that is equal to the whole. Mathematicians would puzzle endlessly at how that's supposed to make any sense at all.

And things will keep getting more and more ridiculous as new technology brings out results that invalidate the whole thing, such as better imaging that shows changes that older technologies simply did not have the capacity to identify.

 

[livinglighter]

Another mind-boggling thing for me is this.

Functional neurological disorder (formerly called conversion disorder) is a mental condition in which a person has blindness, paralysis, or other nervous system (neurologic) symptoms that cannot be explained by medical evaluation.

https://medlineplus.gov/ency/article/000954.htm#:~:text=Functional neurological disorder (formerly called,be explained by medical evaluation.

From what I am currently aware of, when a patient complains of cognitive symptoms linked to the brain, e.g. attention, memory and concentration, the causes are; organic factors, false pretence or psychological disorder. An MRI should be carried out if a patient doesn't have a psychiatric history. If the MRI is clear, the next step in making a confident diagnosis because all three causes require very different interventions and treatments, is a neuropsychological evaluation, as it tests for structural deficits, malingering and psychological disorders. The test carefully evaluates all three possibilities causing someone to complain of varying cognitive symptoms.

For the most part, pwME complain of nervous system (neurologic) symptoms that a range of medical evaluations can determine.

At some point, ME symptoms have been understood to result from malingering. A neuropsych test can determine the likelihood.

As it stands, symptoms are alluded to be some form of converting emotional distress. A neuropsych test can assess the presence of psychological disorder.

Some argue ME is neurological. A neuropsych test can determine if cognitive symptoms arise from structural problems.

The Neuropsychological evaluation will also determine if a combination of the above is present.

https://www.ncbi.nlm.nih.gov/books/NBK513310/

Neuropsychological evaluations require the use of standardized instruments to assess cognitive functions, behavior, social-emotional functioning (i.e., mood, personality), and in certain cases, adaptive functioning and academic achievement. More specifically, cognitive functions can be organized into specific major domains such as intelligence, attention/concentration, learning and memory, language, visuospatial and perceptual functions, executive functions, psychomotor speed, and sensory-motor functions. Given the complex nature of cognition, most standard test instruments measure more than one functional domain, though neuropsychologists have methods of differentiating strengths and weaknesses. Many neurologic and psychiatric disorders have been empirically shown to have specific patterns of dysfunction.
[...]

An important part of neuropsychological evaluations is the use of Performance Validity Tests (PVTs) and Symptom Validity Tests (SVTs) in order to measure for the deleterious effects of suboptimal effort, to feign, and malingering, all of which can impact the outcome of exam results and interpretation. PVTs and SVTs are used in both pediatric and adult evaluations, even when there is no initial suspicion of possible exaggeration or concern for the fabrication of cognitive dysfunction.

Comprehensive assessment typically begins with a detailed medical record review, including medical and psychiatric history, medications, laboratory results, and neuroimaging reports, and in-depth clinical interviews. The clinical interview includes behavioral observations and may last one to two hours.[...]

[...]The reader should note that neuropsychological evaluations are thorough examinations with multiple components and involve much more than the administration of a few tests. A neuropsychological evaluation is not limited to testing but also involves, as mentioned above, a clinical interview, review of medical records, testing current cognitive and academic abilities, tests of social-emotional functioning and personality, adaptive functioning, estimates of premorbid functioning, behavioral observations, and integration of all these components. In addition, the clinician may also need to obtain educational and employment records and conduct collateral interviews with family members.

Neurologists have been using neuropsychological assessments to refer patients without organic abnormalities to mental health services following careful evaluation since, forever. If a patient has significant early childhood trauma causing maladaptive beliefs, shouldn't that be established while undergoing a thorough mental health evaluation?

In some cases, what has been established as FND seems backwards, in that, the patient presents with neurological symptoms but there is a refusal to screen for in-depth structural abnormalities.

TO ADD: I doubt just having early childhood negative/traumatic experiences is enough to justify maladaptive thoughts, there should be some other traits including behavioural ones that point towards a significant level of distress that a neuropsychologist is able to identify during the long period of interaction with the patient. They also work with patients suffering from lots of established neuro-brain conditions so they understand the symptoms and can interrogate them very well.