Distinguishing functional from idiopathic dystonia: A novel approach

Roberto, [00:01:00] welcome to the podcast and thank you for being with me today.

Prof. Roberto Eleopra: Hello. Thank you Micki to invite me to this nice podcast. It's a pleasure to be here with.

Dr. Michele Matarazzo: Okay, let's start, Roberto. Could you briefly frame the problem for us? What is functional dystonia and why is it difficult to diagnose also compared with other functional movement disorders?

Prof. Roberto Eleopra: Yes. Functional dystonia is one of the most common and most diagnostically challenging form of functional movement disorder. This dysfunctional disorder involve abnormal movement that occur without startle nudge of the nervous system. And they are typically recognized by clinical inconsistency and incoherence.

These are the main features that we use for diagnosis of functional movement disorder, but functional dystonia is particularly difficult for the clinicians because, [00:02:00] it closely resembles idiopathic dystonia and sometimes presents an unusual or a typical feature, and also if we consider it the sudden onset, the fixed posture at rest or resistance of passive movement.

It could be hypothetically an a marker for a functional dystonia, but these features could also appear in idiopathic dystonia. So it's very difficult for the clinicians to understand and to identify what's the functional movement disorder. What is the idiopathic disorder? And this is still depends on the experience of the neurologist.

On the clinical interpretation, it is a common disorder. It is different also in the diagnosis when we compare tremor or myoclonus or rather functional movement disorder in which entrainment on some other clinical [00:03:00] semiological features can help us to differentiate these entities.

Dr. Michele Matarazzo: So you were mentioning some of the science that we usually use when we are evaluating a patient with suspected functional dystonia, but as you were mentioning there is a lot of overlap with actual idiopathic dystonia. And that makes it very difficult. And I guess that's a problem also when you want to help the patients because of course the management of a patient with functional dystonia and i diopathic dystonia it's different. And even for advanced therapies, it makes a huge difference. Now, you had a very different approach, which is really original using polyelectromyography with a controlled propofol sedation protocol to see how muscle activity behaves across different stages of consciousness.

What was the central hypothesis? What did you expect that propofol would show would reveal in functional dystonia compared with idiopathic dystonia?[00:04:00] 

Prof. Roberto Eleopra: Yes. This is a start from the pathophysiology of the two different diseases. In idiopathic dystonia, we are thinking that there is a dysfunction of motor network involving the basal ganglia, the cerebellum, the primary secondary somatosensory cortex. But there is also converging evidence point that in functional dystonia there is only a cortical caudal rostral dysfunction without a true interest in the basal ganglia and in network of the deeper neurological center.

And this is important because when you use anesthetic or you want to evaluate the patient during sleep, there is a different feature. There are some data. There are the older publication in which, for example, during sleep and idiopathic dystonia there is a decrease in [00:05:00] muscle activity when you recorded by poly-EMG.

But also in conditioning with there is a reduction of a wake cortical status. There is a decrease in muscular activity. This is not really true for all the patient. But it could be the aim, the main concern about the evaluation during anesthesia, using anesthetic technique.

And in psychiatric, there are also some therapeutic technique based on aesthetic infusion in which there are some relaxing or conditioning training in which some psychiatric patient could evidence an improvement in clinical state. So it's important to understand that if we are able to evaluate the muscle activity as a final output of the motor [00:06:00] system during different awake status, it could be possible.

This is the hypothesis of our study to differentiate functional from idiopathic dystonia.

Dr. Michele Matarazzo: Great. So basically, the idea is that pathophysiologically, the idiopathic and the functional dystonia have a different topography in the brain shutting down different parts of the brain, which happens in different states of the sedation, will reveal some differences in the poly-EMG exam. 

Prof. Roberto Eleopra: Exactly. And the aim of our study, it was to identify a neurophysiological biomarkers, was capable to improvement the differential diagnosis between functional and idiopathic. Because we know that the diagnosis category of the Gupta Lang criteria. There are some missing point and some gaps when we want to identify the true idiopathic [00:07:00] dystonia.

And so if we decide to study well-defined 17 idiopathic dystonic patient in comparison to 10 clearly functional dystonic patient based on the Gupta Lang criteria. In this case we compare and we match by age, sex, education, pattern of the dystonic distribution, the mode of onset, the presence or absence of fixed posture, disease duration, and also the response of the botulinum toxin.

And we also try to compare to match by mood and anxiety symptoms, and we want to evaluate what's happen when you induce as lovely and graduate anesthetic protocol by using propofol. We know that propofol is a prevalent action on the cortical layers, on [00:08:00] the cortical network, and theoretically, if the dystonic is idiopathic dystonic, the main mechanism is subcortical in the basal ganglia and the integration with this somatosensory and motor.

And it could be that is less influential than the functional dystonia when the pathophysiological mechanism is prevalent cortical.

Dr. Michele Matarazzo: Okay, so I get the theoretical idea and the most of the methodology, but I guess a lot of people reading this article was thinking about how complicated the whole protocol is. How feasible is it for a real life scenario? How long did the whole protocol take?

And how many resources do you need to do it? How complicated it is?

Prof. Roberto Eleopra: Yes, the protocol is not too complicate because it is the same protocol that we use when we apply MRI under anesthesia. So it's the infusion of [00:09:00] propofol is no more than 20 minutes. We have a range between 14 and 28 minutes in all the patient is well tolerated, so the patient is safe, and we start with very low dosage of propofol, one microgram for mL for each patient and is not bolus.

It's an increase in two minutes, in step of at least two minutes. And we observe from a clinical point of view that the variation of conscience, but also we evaluate by EEG and the base methods that an anesthesiologist use to understand the deeper anesthetic protocol. And we have only to record this with electrodes in the muscle with a mean of 10 muscle.

So we have 20 minutes to prepare the patient. 20 minute to do the test in usually in 40 minutes [00:10:00] we complete the test and we apply in clinical practice when the patient start the infusion for the MRI and the sedation. It's very useful and very practice to evaluate not only the pattern of EMG, but also the clinical state and what's happened to the dystonic pattern.

Dr. Michele Matarazzo: Great. So, it is time consuming but feasible, nevertheless.

Also outside of the research setting, it's 40 minutes, is not something that you can do on a routine with all of the patients. With selected patients. It's something that is definitely feasible if it is helpful.

Now, let's see if it is helpful. What are the main results of your study?

Prof. Roberto Eleopra: The main results are interesting because of course, it is not is necessary to use in selected patient when we want to understand different questions. But the result is that in a weak state, of course, we have a typical EMG pattern of cocontraction, prolonged [00:11:00] burst, sometime the overflow of the recruitment in muscular involuntary hyperactivity.

But we observe the same in the functional movement disorder. There is overlap of course, in some functional movement disorder there is a variability in the recruitment, but this is not enough to differentiate this kind of population

Dr. Michele Matarazzo: Can I just interrupt you one second? Maybe for some of the listeners who are not really into this, what are, what is the co contraction and what is the overflow that you're mentioning?

Prof. Roberto Eleopra: Okay. The co contraction is when flexor or extensor muscle antagonist muscle have simultaneous contraction that is not physiological. When we flex some body part, there is a contraction of the synergic muscle and inhibition of the opposite muscle. In this case, in the dystonic, one of the [00:12:00] characteristic the neurophysiology want to do with diagnosis is a co contraction between antagonist muscle. And another feature, when we repeat the movement, this involuntary activity extend by a topographic, for example, from distal to proximal part of the links. And this is another feature usually typical for organic, for idiopathic dystonia. This is not usually observed in functional movement disorder, but is not always true because some functional movement disorder there is a co contraction is not easy to understand this variability and this is an important feature.

So what's happen when we do the test during the progressive sedation we didn't observe, not so much difference. All the patient, they tended to decrease the muscle activity. But in functional [00:13:00] movement disorder, when we have a deep anesthesia protocol, there is a complete resolution in 100% of the patient of the muscle contraction in idiopathic dystonia in 53%, there is a persistent of the muscle contraction. So the first thing that interpretation is if he's present, it could be an idiopathic dystonia, but more interesting in when we stop the infusion and there is a recovery in the slow progressive recovery. In a week of the patient, there is different change.

The dystonic muscle reappear the same kind of voluntary contraction in the same pattern at the baseline early before the conscience is completely recovered. In functional movement disorder, there is a prolonged silence and when appear, [00:14:00] usually during the reappearance of conscience, the patterns change from the baseline.

And so these two main point at complete deep sedation and during the recovery is very useful to differentiate this kind of dystonia, this idiopathic dystonia for functional dystonia.

Dr. Michele Matarazzo: This seems really useful for this doubtful cases that we sometimes, as you were mentioning, is difficult to differentiate functional from idiopathic dystonia and now you showed this in this study. Obviously this is very interesting, this is very novel, but do you think we should use this in clinical practice already?

Do we need more evidence or this is enough?

Prof. Roberto Eleopra: Of course I agree with you. This is a pilot study. There are some limitation. The first limitation is the sample size because we have only 17 patient and 10 patient with functional dystonia, and also we select [00:15:00] patient in which the diagnosis. But from a clinical point of view, it was a certain, but if we are some unclear cases, we have to validate this test because probably it's appear more useful when there reason we are not able to differentiate a clear functional movement disorder from an idiopathic dystonia.

The first things is validating a more simple science and to include the more defined, definitive case of functional idiopathic dystonia. And also we are trying to better quantify the EMG pattern because it's only a qualitative observation until this moment. Of course we use a blinded neurophysiologist in order to understand what's the pattern of EMG without evidence of functional, of [00:16:00] idiopathic dystonia, but we have to validate from some other quantitative measures.

Dr. Michele Matarazzo: And one thing that was interesting while I was reading the paper is that you not only used the EMG, but also the passive manipulation during this deep sedation. So the very clinical hands-on literally clinical aspect of this. Can you tell us a little bit what happened with the passive manipulation?

Prof. Roberto Eleopra: Yes, this is important for the clinicians because when you have a fixed posture, sometime we are not able to understand if it is a true dystonic posture or there is a retraction from tenderness or some osteo skeletal change in bone. And so when the patient is under deep sedation, we are able to have a passive movement of segment of part of head.

And it's easier for us to understand, for example, if a patient with a fixed posture [00:17:00] could be a benefit from botulinum or for DBS or from some other interventional therapy because if there is a retraction from bone from some other osteoarthritis, this a limitation to obtain a clinical improvement of the posture.

Dr. Michele Matarazzo: Perfect. We're getting close to the end of this interview. I wanted to ask as you mentioned already this is a pilot study. There are a few limitations, one of them in the sample size. And so you said already we need to validate this in a larger cohorts. Are you working on this or do you expect someone else to do it?

Prof. Roberto Eleopra: We are working on this. We are improving the sample size and also we are including some uncertain keys in order to understand what's happened. And in particular, we are also trying to understand if there is some differences between genetic form of idiopathic dystonia and [00:18:00] non-genetic form.

Because we know, for example, with the micro letter recording during DBS, it could be possible to observe a different electrophysiological pattern in genetic and in other different form or primary dystonia, non-genetic. So this is what we are doing now in order to validate, to improve our data.

Dr. Michele Matarazzo: Roberto, thank you. Thank you so much for joining us. Congratulations for your study to you and your co-authors. This is a really thought provoking pilot study. Thank you.

Prof. Roberto Eleopra: Thank you for invite me and for all the listening people that you are here with us.

Dr. Michele Matarazzo: And for our listeners, we've been discussing the paper published in Movement Disorders Journal titled Poly Electromyography Under Propofol to Differentiate Functional From Idiopathic Dystonia: A Pilot Study. Thank you all for listening. [00:19:00] [00:20:00]