The FND Society Podcast
Welcome to the FND Society Podcast, a series tailored for clinicians and researchers in the field of Functional Neurologic Disorders.
The podcast covers a wide range of topics, from basic science aspects like neuroimaging and biomarkers to clinical practice issues such as diagnosis, treatments, and outcomes. It also explores how FND is understood and treated within the current medical and psychological paradigms, with a goal to enhance knowledge and awareness across the medical community.
Our goal is to make this a valuable and accessible resource for professionals, delivering the latest research in FND through engaging conversations with experts in the field. We aim for this series to be a practical and informative experience, connecting listeners directly with groundbreaking developments and insights in FND. It's our hope that each episode will contribute meaningfully to your professional knowledge and understanding.
For more information about the FND Society visit: www.fndsociety.org
The FND Society Podcast
Selma Aybek: Identification of biopsychological trait markers in functional neurological disorders
Use Left/Right to seek, Home/End to jump to start or end. Hold shift to jump forward or backward.
In this episode we speak with Dr Selma Aybek about her pathway into FND research, neuroimaging in FND, the implications for reducing stigma and unhelpful historical dichotomies or dualistic approaches in mind-body disorders. Next, we discuss the utility of lumping vs splitting given the heterogeneity of FND, as well briefly discussing outcome measures, also capturing comorbidities, and patient quality of life.
Related Links:
Research: https://www.unifr.ch/med/fr/research/group/aybek/
Clinic: https://www.h-fr.ch/annuaire/selma-aybek-rusca
Webinars | FNDS (fndsociety.org)
Welcome to the Functional Neurologic Disorder Society Podcast. I'm your host, Erica Cotton, coming to you from Chicago, Illinois, with a special thanks to Michael Romeo, our production engineer coming to us from Australia, and our content curator, Ingrid Hurzauer, from the UK. This week's guest is Dr. Selma Ibeck. She's a full professor of neurology at Freeburg University, Switzerland. She is chair of the Committee on Research of the American Neuropsychiatric Association and aims to foster international collaboration in research and medical care of mind and brain disorders. In this episode, Dr. Ibeck and I briefly discuss her pathway to F ⁇ D research. We then spend a good deal of time discussing neuroimaging in FND, specifically the implications for reducing stigma and unhelpful historical dichotomies or dualistic approaches in mind-body disorders. Next, we discuss the utility of lumping versus splitting given the heterogeneity of FND, as well as briefly discussing the role of outcome measures and the importance of capturing comorbidities in patient quality of life. I will caveat that we are engaging in an academic discussion of these topics, and some of these discussions may appear blunt or direct to a patient-centric audience. Also, all views and opinions discussed in this podcast represent those of the host and respective guest, not any position or policy of the Functional Neurologic Disorder Society. And with that, I will lead into my discussion with Dr. Adek. So thank you so much for joining today. As a start, why don't you begin by telling our listeners about your academic background, how you arrived at involvement with FND and your work, and which career path you're on.
SPEAKER_00Okay, thank you. It's a pleasure to talk about FND uh today. So, how I arrived uh to FND, it was through my clinical practice to go straight to the point. Because I actually already at med school I was interested in how the brain functioned. I decided to go into neurology specialty because I was fascinated at med school by some neuropsychology uh lectures. And so that's why when I started neurology already, I had this view that behavioral neurology or neuropsychiatry was the field I really wanted to go into with this non-dualistic view that uh psychiatry and neurology both involve the brain. I did my MD, uh my medical thesis actually on the um uh consequences of emotions, uh changes in emotions after stroke. So that was the first really link between emotion, psychological factors, psychiatry, and the brain. And then um F and D really came of interest when I saw patients. So that was a bit later in my training when I saw many, many of these patients. And I was at the time uh doing the outpatient clinic where we were referred to the most difficult patients, let's say, at this university hospital. And so we saw these patients where neurologists didn't know really what diagnosis to make. And one of my mentors opened my eyes by showing me the first clinical signs that we now use routinely, these positive signs. But at the time, it was really this fine neuro exam that I loved. So, first of all, I think I liked this clinical part of examining F and D patients. And then I was fascinated by the fact that actually we did not understand much about what was happening to these patients.
SPEAKER_01That's excellent, right? I I think a lot of people have come across it clinically, didn't intend to, and then kind of stumbled across it clinically and then just became fascinated by the unknown mechanisms, um, presentations. How do we capture it? How do we describe it? Um, and then importantly, well, now how do we even treat it? Which are all aspects we're going to chat about in just a minute. Um, but importantly, you co-chair the research committee on neuroimaging for the FNDS Society with David Perez. Would you mind chatting briefly about the role of neuroimaging in FND and where you see the utilities as well as any potential pitfalls or hurdles we need to overcome to really start to capitalize on those research methodologies?
SPEAKER_00Yes, neuroimaging is really key, I think, in helping understand FND. And actually, I like to refer back very often to the work of Jean-Martin Charcot, who is considered the father of neurology, because he himself, when he described the mechanisms potentially at stake in FND, he said that it might be due to a dynamic functional lesion that we cannot see right now because it escaped our means of investigation. That's how he wrote it. And he also added that one day maybe we will have a microscope that is powerful enough to capture that uh dynamic function. So actually, we now have these microscopes in the form of neuroimaging. So it's been now around 30 years that we have neuroimaging, and there has been a lot of progress in understanding, in destigmatizing this disorder, in trying to understand what's happening in the brain of these patients. So that's why I feel very privileged to be uh now co-chairing with David Presley's Committee on Research. Uh, we see our role here as bringing together international experts in making progress on how to further advance the field of neuroimaging in FND.
SPEAKER_01I think it was a very prescient finding that you stumbled upon there, which is FND in a lot of ways has a dysfunction that we can't yet quote unquote see on typical clinical neuroimaging evaluations. But when applied in a more research methodological fashion, we can see group level differences. Where do you think the barrier is, or how far away do you think we are from being able to use those group level methodologies of brain regions, brain size, brain connectivity, from being able to use that in a clinical sense, like we would a traditional MRI to identify brain tumors or lesions or the more traditional large-scale neurologic issues that we can now more readily identify, but I think we're still lagging in the small scale. How far away do you think we are from individualized neuroimaging for patients with smaller scale brain dysfunction?
SPEAKER_00Yeah, that's a very good question because there are two ways to see neuroimaging in FND. One is really to design studies to help us understand the mechanisms underlying the disorder. So the really the patrophysiology. And there's another area of neuroimaging that we could, and I think that's what you're alluding to, that we could potentially one day use as a clinical tool, because right now we don't have any marker to help us with the diagnosis. Of course, we have some for some subtypes, like for um non-epileptic uh seizures or functional seizures, we can have the help of the electroncephalography. Uh for tremor, we also can have um tremor recordings, but for other types, we don't have any uh exam that helps us. So uh we are developing, we did actually uh two studies that try to see if the use of resting state MRI, which is very good because patients just lie in the scanner and they don't need to do anything, they just uh look at a cross on a screen and relax, and we see how their brain is uh how the how the brain connects regions to one another. And with dysfunctional connectivity, we were able to see that with machine learning and artificial intelligence algorithm, we can make the difference between a brain that looks like a patient or a brain that looks like a healthy control. Now you're asking how far are we to use that in clinic? I think we're pretty far. I think we're far because we need a lot more validation, and also we have to be extremely careful not to go down the road to think that this will be the answer to make the diagnosis, because the diagnosis is still clinical. We need really excellent clinical skills to do the diagnosis, not only for the neuro exam, I just mentioned the positive signs earlier, but also the whole history taking, uh the whole context in which FND appears. So, and also I'm not saying at any point that neuroimaging and artificial intelligence will one day replace the clinical diagnosis, but I think in some cases it could help when the diagnosis is difficult. And another area where it could help is um possibly for the recognition of the disorder when facing entrance policy, benefit policies, uh, because it would help to have a biomarker, I think. And with that, I can add a third important point is that it would also help destigmatize the disorder. It's still so much stigmatized that um patients say, okay, we don't see anything, so it's hard to understand this famous dynamic lesion of Shark Co. So being able to see it on a scan, on an imaging, uh, on such a tool, I think could help a lot to understand that there is also some biology to the disorder.
SPEAKER_01I agree completely that it's not just in quote unquote someone's head or that they're not making it up and that it does have an actual biological correlate that is happening. I've always found that term quite interesting. It's in someone's head. I was like, well, anatomically, that is correct. It is coming from their brain. So they're not wrong with that. They're just, they don't realize that they're they're actually being very ironic in that statement if they're making that level of misunderstood uh attribution. Um, the other piece I agree with, including um reducing stigma, but I think you're 100% correct in that just having a biological marker or a neuroimaging correlate does not eliminate the need for clinical assessment, clinical characterization. As one of my mentors said, the tail doesn't wag the dog. Um so for a lot of neurologic conditions, we use neuroimaging as an additional feature to aid in diagnostic understanding, diagnostic certainty, or an element of diagnosis and treatment planning. But basing a diagnosis solely on neuroimaging, yes or no, in this binary distinction, it would be inconsistent with most clinical practice in neurology or many fields of medicine to base it solely on imaging parameters. Um I think there's definite, if we do have it, that would be useful for stigma and potentially useful for diagnosis, but not replacing a good clinical exam and the positive findings that we have. Um, there's also, I think, another common misunderstanding of sort of divergent intents with neuroimaging for understanding a mechanism, right? And targeting a research setup or a research design that differentiates mechanism that's designed to answer a hypothesis-driven scientific question versus having a neuroimaging paradigm that is in a way orthogonal, in meaning to broadly capture a single feature of an illness that might be diagnostically indicative. And actually, those neuroimaging paradigms might be very different or need to be developed in very different ways because you can't just necessarily translate a research study into a clinical diagnostic tool that broadly captures or is is has high sensitivity or specificity to a clinical concept, which is different than differentiating components of an illness from it from within itself or from a hypothesis-driven mechanism, which I think a lot of people might misunderstood, think, well, neuroimaging is neuroimaging, right? And if you do the neuroimaging this way, then it should apply that way, right? You know, research and clinic, it should just all be the same thing. Any any thoughts about how to answer those sort of hard questions or people might have about why doesn't the neuroimaging methods you use for research translate to you know the clinical process?
SPEAKER_00Yeah, actually it's interesting because I have many patients who ask for that. They say, oh, but I've seen on your website you're doing imaging. I want my imaging scan, and I always have to explain, yes, we can, but that's only in research protocols for now. It will not bring any answer to your particular case. Because those algorithms that I was mentioning of machine learning are, like I said, not ready for clinical use at all. It's only at group levels and statistical levels. So yeah, we have first to make people understand that. And when I was saying we're far away from clinical application, it's because there are just a few studies, maybe four or five. Like we've done it in my research group. Some other groups have done that also, uh, the same classification of healthy people versus F and D patients. But of course, in a clinical setting, this is this will never happen. You don't struggle to identify a healthy person from an F and D. So these are steps just to do validation. The next step of the validation would be to see first the inter-scanner variability. So if I scan a patient in Switzerland and I use a classifier, can that be done also in the US, in another country, and so on? So this would be a first validation step. We have some evidence we did validate across four European centers, and our classifier worked. But we need more to do that. And the next step would be to then uh compare, let's say, a patient. Uh, if we have a doubt about a functional dystonia versus another uh kind of dystonia, here we would have to validate also those machine learning algorithms with another control group. Um, so that's why I'm saying we're still far away.
SPEAKER_01I know, yeah, and it makes perfect sense in that regard. The other sort of not barrier, but perhaps hindrance, encumbrance that that I imagine or or I've questioned in in regards to FND is I also feel like from a clinical standpoint, we we've gotten fairly good at identifying structural abnormalities or larger scale structural abnormalities, you know, with um things like MRI or CT, where we can assess fairly reliably structural integrity at a large robust scale, um, or EEG, right? Again, a larger scale electrical phenomenon happening within the brain. But I I attended the Society for Neuroscience annual conference just a few, gosh, maybe a month ago now. And one of the main themes of that conference was understanding network connectivity. So we've kind of got more cellular idea and we've got the big scale on brain imaging. You know, is this large structure intact? We kind of have a better understanding of how cell-to-cell communication works, somewhat-ish. Um, but bridging that middle gap of connection and brain regions talking to each other, I still feel like we don't have as clear an understanding. I don't think anyone would agree that that's probably an understatement. We don't have clear understanding of how large networks communicate, the roles and dynamics of that and potentially the impact of disease. And I feel like that's where FND's model or FND's hypothesized mechanisms that we have, that's the realm in which we think it falls, right? In this network connection disorder rather than one brain region that we can localize and assess, is it structurally sound? Right. And I wonder if that's also part of our limitation with FND is in order to understand FND, we first have to have better understanding of the underlying networks. We're still building an under an understanding of underlying networks within the brain, as well as how to measure those reliably outside of a research setting in a clinical setting. And FND, unfortunately, is somewhat needs to be carried along with the understanding of these larger networks like salience networks and motion regulation networks. Um I don't know if you have any have had similar thoughts or um also see that as a potential rate limiting step for our understanding of FND.
SPEAKER_00Well, I think there are fantastic progress in neural imaging techniques. Like I said, we have those tools like only 20 to 30 years. And first they were the SPECT scans, PET scans, and then we have the MRI, and now we have also have other ways to analyze them. Now I'm referring to functional connectivity. Uh, the classical way to look at it is to look at the um static connectivity between two brain areas, but we also have now dynamic connectivity, so to show uh in a way a brain state, how those brain states vary uh in time. So there are a lot of things we can do in trying to uh better understand uh what goes wrong, if I can say like that, in the brain of uh FND patients. And so I'm still hopeful also that we're we're making progress because we might sound a bit negative now when we're saying all these validation steps. I think science and research is going fast, also, and uh neuro neuroimaging scientists have made fantastic progress that we now, as clinicians, can also apply to our patients. And you're referring also to structural um imaging. This is also quite new now that a few studies have shown gray matter and white matter abnormalities in F and D. So, you know, it questions this whole, again, uh Jean-Martin Charcot idea of dynamic lesion. We might even find uh brain uh anatomical changes uh that might help us understand the disorder. And when I say might help understand, I'm referring to possibly vulnerability factors. It could be that certain brain area are maybe we are born with different volumes of certain brain areas that could cause the disorder, or not only that, because it's never one cause, like many neurological disorders, it's multifactorial, but could play a role in the cause of the F and D. Or it could be a consequence of uh having a symptom for a long time and just reflect a plasticity phenomenon. And I don't think we have the answer yet, because we need longitudinal studies for that. We need to see a cohort if we identify one region of the brain that is smaller, let's say, or bigger. We need to see how it evolves over time. Does it stay like that? So was it there already? Is it what we call a trait marker or a vulnerability marker? Or is it more a plasticity or a state marker? And these are fascinating research questions. Now I can refer back to this neuroimaging committee uh that we are co-leading with David Prez. I think it's a fantastic opportunity to do large-scale studies because uh most of the studies that are out right now in neuroimaging are roughly um the sample size is roughly around um between 20 and 50 participants, let's say. So pretty small, uh, given also the heterogeneity of the symptoms we're studying. So within the F ⁇ D society, we might have this opportunity to bring together experts and conduct uh multi-centered studies, larger studies, bigger uh initiatives, and this will move forward to the field.
SPEAKER_01No, it it's wonderful to have access to that cohort and potentially a larger sample size to start to answer some of these questions. And one thing that I love is probably the wrong word, but I find encouraging or exciting about FND research as well, is it it does beg seeing structure and function along a continuum rather than discrete dichotomous variables. And I think FND does land squarely in the middle, forcing us to abandon, not necessarily fully abandon, but at least highly question um traditional paradigms that might view structure or function as fully independent or separate phenomenon, which I think is good. I think for a lot of psychiatric conditions, you know, as a neuropsychologist working more with a broad range of psychiatric conditions and the differences between, you know, and a lot of neurologic conditions that might be more structurally based, like a stroke or a traumatic brain injury that damages tissue versus a psychiatric condition that has an underlying functional difference, but does have a structural change and not viewing those as discrete or distinct or non- as mutually exclusive or non-overlapping versus a continuum where there's overlap and function drives structure, and structure can drive function in this dual relationship that becomes heavily married, especially when you approach the middle ends of those spectrums, which I think is wonderful not just for F and D understanding, but also more broadly for a range of neuropsychiatric conditions and advancing and reducing that split that's happened between psychiatry and neurology, that this chasms that's formed that says that they're they're distinct and different. So I actually really think it's in some ways beneficial to broad practices of neurology and psychiatry and neuropsychology to have a condition that So definitely forces abandoning some of those dichotomies that we've had for a long time, that I think has probably stalled some progress or understanding.
SPEAKER_00Yeah, and I can hear say that the all the neuroimaging studies that have been done with task fMRI have helped in exactly what you're saying, reduce this dichotomy or dualistic view that there's the psychiatry part and the neurology part, because there are studies also looking at how emotions are dealt in the brain. And this is good not only for uh advancing research, but I think it's very useful when you talk to patients. I like to tell the patient sometimes that, you know, uh there's a problem in the brain, and like you said, it's in the head or in the mind. Uh often patients come and say, by the way, um, I've been told it's all in my mind. So they they bring that to my consideration. And then when we start explaining the potential mechanisms of FND, I like to tell them that research in neuroimaging has shown uh abnormalities in how the brain deals with emotions and in the areas of the brain that deal with emotion. And here I'm referring to the limbic system, of course, uh, and also uh a problem in the way the brain deals with sensory symptoms, integration with motor control. And here I'm referring to the sense of agency and the agency network, and that they are connected. That some studies have shown that there is a sort of short circuit between the limbic system and and other motor areas. So I think it's also useful to uh when we explain to the to our patients what's happening in her.
SPEAKER_01Exactly. Like any you know, human illness, and an answer in and of itself adds adds a degree of comfort and and confidence, or at least you know, some solace for the symptoms that are being experienced versus it remaining an unknown mystery, which is I'm very grateful for FND sort of necessitating that we have these nuanced conversations and embrace a more nuanced way of considering human behavior and um symptoms and brain function, which is great. On that line, as a limitation, well, not limitation, but perhaps a consideration for neuroimaging research as well as clinical practice, um, becomes somewhat of uh lumping versus splitting of the heterogeneity, right? Where patients can come in with such a range of symptoms, um, seizure in large categories, right? Seizures, movements, cognitive concerns, sensory symptoms, dizziness, et cetera. Um, and whether or not we consider looking for shared mechanisms underlying all FNDs, whether it's useful to look at the phenotypes of each specific symptom and how far do we split that down? Do we lump them into large categories, into more symptom specifics? Um, and also the challenge of I think singular presentations are rare and mixed presentations are much more common in this very heterogeneous way, which does present some interesting challenges when it comes to traditional research that likes to parse everything out into these nice, neat little boxes that are that are highly um uniform or or segregated. Um but I'm just wondering how you and especially um the neuroimaging research task force for the FNDS have thought to approach that um the heterogeneity question of FND when it comes to neuroimaging.
SPEAKER_00I know, hard question. Yeah, but you're mentioning uh splitting or lumping. So I'm a clear lumber. I think uh it's useful uh at two levels to lump the different subtypes of FND together. One is uh research-wise, like you said, the other one is uh on the clinical side. So if we start with the research, uh I think it makes sense. Um because it will, like you just said, it will help us if we find a shared mechanism across all of them. Um because also they probably share the same risk factors, all of these subtypes, and having a common mechanism, I think, is the aim. And only then it will become another research question once we've understood better the core mechanisms of but why now does this patient have a weakness and then later a tremor? And the reason also we need to lump them, I think, is that uh usually or often, let's say, the same patient will have different subtypes. So we can see a patient that will come to see us first because they have a dystonia, and then later on they will develop a weakness or a functional seizure. So I think it really uh belongs to the same disorder. Now, um clinically, also, I think we need to lump them because the expertise that we develop by seeing these patients uh can be applied to all subtypes and should be actually. The way we talk to patients, we explain the diagnosis, we approach the whole uh um follow-ups. It makes sense to do it for all subtypes. Uh I think it's uh it's a um a waste of resources in a way if we only see functional seizures patients and not uh abnormal movements. And this belong together. So that's why I'm a strong lumper.
SPEAKER_01I love that strong lumper. Um I would have to agree with the clinical as well as but research utilities of I think the lumping principle. And I there might be some use in in splitting, but I think especially to start where where you're discussing where we're at with this condition and still developing paradigms and understand trying to, in early stages of identification, lumping just seems to make the most sense. Um, and then maybe later on, once we've got a clear understanding of all the shared variances and the shared risk factors and shared aspects that we can target with treatment, then maybe it might make sense to attempt to fine grains, split some of these phenomena down into their different pieces if there's a degree of divergence across treatment responsiveness or um treatment or um disease trajectory that might happen when we consider splitting, and if if that's relevant or not, and we might find at the lumping stage that those diverge, those smaller features that we might split out actually don't contribute to the shared um disease progression or treatment responsiveness, which I think are central questions now. So I'm pleased to hear, hear the lumping, but I'm obviously of a shared, shared mindset and might have my own bias there. Um the other, the other piece that um has often come up as well, I think farther outside of individuals with clinical experience with FND, um, or who have a more historical model of FND, would be relate to diagnoses I would consider sort of on the fringe or adjacent to FD, like historical conversion, fictitious disorder, malingering. And again, I would tend to lean to view those more on as a neuropsychologist, more on more on a spectrum of presentations and mechanisms. But I'm curious from from your work as well, can you maybe share with our listeners how someone who raises that concerns of well, aren't well, isn't this just malingering? How do you differentiate this from fictitious? And and where do we draw those lines in in the sand, so to speak?
SPEAKER_00Yeah, so I think there are lines that can be drawn. For example, one line that uh can be easily drawn is the uh difference between malingering and all the rest that you mentioned, because malingering is actually not a disorder. It's not uh a diseased person, it's just a dishonest person that has a purpose, that wants a benefit, that will consciously uh try and deceive the doctor or the inference people or or whoever.
SPEAKER_01It's willful behavior, will willful directed, goal-directed behavior, although malignant behavior. Exactly.
SPEAKER_00Whereas when we enter fictitious disorder, it's a disorder. It's defined that uh it itself uh in it is self-inflicted. So an example would be a patient who comes with dilated pupils because they actually put some drops in their eyes, but they go and see the doctor. Why do I have those large pupils? So it's it's self-induced. But the idea is that it's seeking for help. It's still seeking for medical help, and there is an underlying psychiatric problem. So this entity, of course, needs our attention, and we need to understand why is this behavior coming in a way. So this belongs to psychiatry. Now it's completely different still that what we see in F and D FN D people have genuinely no control on their symptoms, or they themselves say I have partial control. And I think the reason we so often still talk about malingering when we talk about FND is because of the clinical presentation. The clinical presentation is variable. So we can see a patient that is unable to move one leg or one arm, but then an hour later or even a few minutes later, we'll see that this patient is able to walk normally or to move the arm normally. So, of course, lay people or people who don't understand the brain, how the brain works, will say, huh? So there is no weakness, there is no tremor, and so it must be maling grained. And I think it's just due to that clinical presentation. But we otherwise have no no no reason to doubt what our patients are saying. And well, possibly another factor is that uh relate to what we've we're just talking about, that there are no biomarker. If we had a biomarker, uh that would be easier. But uh let us remind us that um a lot of neurological disorders and psychiatric disorders don't have a biomarker. And um, interestingly enough, in the DSM, um it's only in the diagnosis of conversion and FND that there used to be this criteria, not anymore in the DSM 5, but previously in previous version, in the diagnostic criteria, it was always stated uh this is not uh malingering or this is not intentionally produced, but this could be done, I guess, for all other psychiatric disorders, uh, because uh in psychosis you don't have any clear biomarker as well. But uh we don't put this, oh, we have to prove that this patient actually has hallucinations. So it sticks to F and D, possibly because of this of this uh clinical presentation, and uh because people, when we don't understand mechanisms, we tend to reject them. So we don't understand why a patient would have at some point a weakness that will then uh resolve uh later on. And the easiest way is to say, oh, it's incongruent to a lesion of the motor system, and then we jump to this conclusion it could be malingering, and this still sticks a lot to this stigma of patients. But luckily now, with a lot more research, I think we're moving away from that. I'm pretty confident that we're really now in a good position.
SPEAKER_01Yes, and and able to make much stronger arguments, especially with neuroimaging showing these differences. Um, and it's so interesting that you bring up, you know, we don't have this proving of symptoms in other psychiatric conditions, they're just thinking, you know, with anxiety. No one needs to prove, no one questions if someone's anxiety is variable across situations. I get anxious over this test, but then when my boss gave me this assignment, I didn't get anxious. And it's like, well, wait a minute, now are they malingering their anxiety? There, there's something really specific and unique to perhaps the neurologic type presentation of a motor symptom or a seizure-like episode or a cognitive lapse that we really latch on to as atypical somehow. But in a lot of ways, you know, variability is so common across psychiatric conditions and neurologic conditions, less so I think neurologic, somewhat. I mean, but especially psychiatric conditions. I can't think of a single psychiatric disorder that is pervasive in every situation, at every moment you get the full penetrance of the psychiatric phenomenon, right? Or even like psychosis or delusional disorders. Like, why delusional or paranoid about this, but not that? And no one questions if there's any intent or volition. The other interesting thing, I think, also that FND brings up, which again, I'm I'm somewhat grateful for having to bridge these historical limitations or belief factors is around the role of agency, right? Because it's so interesting. There's there is this variability where at times they're able to produce the desired motor outcome or consciousness outcome in a seizure disorder, et cetera. And then at times they're not. And that's what we target with treatment. We target gaining more control and agency over being able to influence that so that it can become, in some ways, effortfully controlled. And I think that shift from lack of control to control really just doesn't sit well with a lot of people in a traditional medical community of like, wait a minute, either you're sick or you're not. And either you can or you can't. And there's this dichotomy, black and white distinction versus this spectrum of control versus lack of control, as well as consciousness in voluntary versus involuntary, as well as those networks aren't always clear and distinct within the brain. And I think FND really brings all of those nuances of brain function into clinical practice in a way that other conditions don't. I mean, I just attended a my fellow gave a delightful lecture on the basal ganglia this morning. And it was, you know, how you need both inhibitory and excitatory things working together within the basal ganglia, right, in order to execute purposeful movement. But how do we define involuntary versus voluntary? And when we think about that. And I think FND forces us to consider those things thoughtfully and not make these hard or fast conclusions about what's voluntary and involuntary and what can be influenced or non-influenced in a way that perhaps other conditions don't. But and and again, I also wonder how much of our bias about that might be trained versus untrained, you know, from from our medical, from our different backgrounds and trainings.
SPEAKER_00Yeah, yeah, I fully agree. When you're mentioning spectrum versus drawing a line, uh I think clinically we can draw lines and we should, and we really have to stop doubting our patient. Now, when it comes to mechanism, you beautifully now uh summarized how it's not I can, I cannot. It's a spectrum and the the the volitional control of movement, or what we call free will, it's actually a very complex brain mechanism. And there is now a lot of research. You mentioned agency, there's a lot of research showing how just a simple movement like reaching out to grasp an object needs a complex brain mechanism of predicting the movement, and then comparing what has been done of this movement to the feedback that the brain receives of that movement that just occurred. And this all has to match. And the mismatch between that, between the intention and the action, can lead to this confusing feeling. Oh, was I the agent? Was it me? Was it not me? Did I control my movement? And this is really complex. And this is something that we now study a lot in in the field of F and D, on those predictive coding of what I uh expected and what I receive as a feedback that uh influences my control over my body. So we are also making a lot of progress here in understanding why patients report that they cannot control the tremor, for example, uh, when uh we see that sometimes the tremor completely stops. So here also we're really moving away from from these dark ages when we could not understand anything what's happening, hence we said, oh, it must be malingering, to oh no, actually, it's a system in the brain that's dysfunction. Yeah.
SPEAKER_01In in an interaction of the complex systems of the brain, not not, God, I'd hate to call a lesion simple, um, but that's probably an oversimplification of it. Um, one other piece that that's um I want to wrap up with is in in addition to understanding the mechanism and targeting these different mechanisms of treatment is also measuring outcomes. You know, I think for a variable condition, it's particularly hard to not only capture phenomena where, by definition, these symptoms are variable. And so measuring them pre-any intervention and then post-intervention, how are we capturing? And the ways to capture improvement, there's patient-reported outcomes, there's symptom-reported outcomes, there's neuroimaging markers across, you know, kind of a whole spectrum of ways to show improvement. Um, but in your opinion, what do you think is is central when it comes to capturing outcomes and improvement or what we should be considering for these patients?
SPEAKER_00So for outcome measures, uh, there is now a new validated scale, the uh FMDRS, that captures really that has been validated for FND, that will capture the severity of the symptom, taking into account the fact that the symptoms are not uh can be intermittent, variable, not always there, and can be on one limb, on another one, on other body parts. So the scale nicely capture all of these elements in one score. So this is extremely useful uh for the follow-up of patients if we need absolutely a number and for research purposes. But now, of course, this is limited to the symptom. Or we know also that patients don't just have their core symptoms, they also have a lot of comorbidities, they have pain, they have fatigue, um, they have an impact on their social life. So, of course, like you said, we'll need to measure that also, the impact of the symptom or the impact of the disorder on the daily life. So, when it comes to outcome measures for research, we need a range of outcome measures. We need to measure the symptoms. Uh, so the FMGS, for example, when it's motor problems or the number of seizures, if we're talking about functional seizures, but we need the other outcomes. And the clinical trials that are out there, I will cite the CODS trial, for example. It beautifully showed, I think, that uh despite uh the primary outcome not showing really um a huge uh the huge desired effect, the secondary outcome measures showed that it helped the patient. So, in terms of quality of life, etc. And this mirrors what we see in clinic. We see some patients that actually, I followed a lot of patients that actually a year later, they're a lot better, but better on what? They sometimes still have their um weakness or their tremor, but they went on with their lives, they went back to work, they have hobbies again, their mood is better, and they're completely transformed, even though they still have the symptom. So we need to take that into account also when we do research. Our aim is not to be symptom-free. Our aim for our patients is that they regain their life and some function and social life.
SPEAKER_01Yeah, actually, I had a follow-up with a patient, and they again they'd had symptoms for a very, very long time. And their symptoms minimally, you know, on the CGI, it was like minimally improved. Not very much, you know, but minimally, not nothing. But they said, but you know what? They're like, I figured out I can still be happy with FND. And that changed my world. And it was just such an empowering piece. Not that, you know, the goal and hope is obviously some significant symptom reduction or symptom elimination where possible, but that's and for a lot of patients it happens. Right. But but for certain a subset of patients, it it is through no fault of their own, not due to lack of trying or lack of effort. Certain diseases or or di presentations are more resistant and regaining that quality of life is is so powerful and important. Yeah, and it's it's interesting as well when I think with a lot of research paradigms, you know, sort of try to screen out or filter out all of those comorbidities and get sort of the pure or clean presentation. And I just don't even think that's probably possible with FND to really find a patient who only has one symptom, one category of one symptom and no comorbidities, you know, of pain or fatigue or anxiety or depression or insomnia. Um, that I just don't even think that would be possible, which is, you know, I'm very pleased to see for most research studies that are currently happening, there's broad inclusivity of comorbidities and considering those as not only important features of individuals to consider, but also how they relate to treatment outcomes and possibly these treatment mediating or moderating factors, which is just so important in an already complex condition that presents with additional comorbidities, and needing to really look at the whole forest and all the trees rather than just a few of the tiny little branches or leaves that might happen.
SPEAKER_00Yeah, with regard to outcome and prognostic, there are another category also of patients. So there are the patients that are symptom-free, that's great. Some other that still have more chronic symptoms, but there are also patients that completely recover and then they have relapses. I've recently also seen a patient that she's known for FND for years, she's back to her normal life, and she had again an acute episode of uh paraplegia. She needed again hospital stay, but very quickly she recognized the disorder, she knew, she knew how the rehab goes, and it went fast very well. So we also see these patients that uh have those relapses, and we are that the medical team is still there to accompany them. So that's why outcome measure again, it can be a chronic disease with which we also can live very well. This is not sometimes some something we also say to MS patients, right? We also say, you know what, there are a lot of people that uh live with their MS. And um, I think people with FND can also live their normal lives, uh, even if they still have sometimes symptoms.
SPEAKER_01Yes, exactly. And offering that hopefully.
SPEAKER_00Oh, but I'm not meaning that in the sense that it's forever. Uh, we see patients who recover or don't have relapses for a long time, but that's also a scenario that can happen is uh to live with FND.
SPEAKER_01Yeah, wonderful. Well, I've really, really appreciated our conversation and hearing all your different thoughts and insights about FND and your brilliant work. So thank you so much for this conversation. And I'm sure our listeners will also agree with me in thanking you uh for sharing your wisdom and insights already and appreciate all the work you're doing and look forward to more. So thank you so much. It's been a pleasure. Thank you. And that concludes this episode's podcast, and we hope you join us again next time. As promised, here's a code for 50% off of the first year membership to FNDS for our listeners. Code FNDS002
