Episode Description
Paroxysmal movement disorders refer to a group of highly heterogeneous disorders that present with attacks of involuntary movements without loss of consciousness. These disorders demonstrate considerable and ever-expanding genetic and clinical heterogeneity, so an accurate clinical diagnosis has key therapeutic implications.
In this episode, Kait Nevel, MD, speaks with Abhimanyu Mahajan, MD, MHS, FAAN, author of the article “Paroxysmal Movement Disorders” in the Continuum® August 2025 Movement Disorders issue.
Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana.
Dr. Mahajan is an assistant professor of neurology and rehabilitation medicine at the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the University of Cincinnati in Cincinnati, Ohio.
Additional Resources
Read the article: Paroxysmal Movement Disorders
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Social Media
Host: @IUneurodocmom
Guest: @MahajanMD
Full episode transcript available here
Dr Jones: This is Doctor Lyell Jones, editor in chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.
Dr Nevel: Hello, this is Dr Kait Nevel. Today I'm interviewing doctor Abhi Mahajan about his article on diagnosis and management of paroxysmal movement disorders, which appears in the August 2025 Continuum issue on movement disorders. Abhi, welcome to the podcast and please introduce yourself to the audience.
Dr Mahajan: Thank you, Kait. Thank you for inviting me. My name is Abhi Mahajan. I'm an assistant professor of neurology and rehabilitation medicine at the University of Cincinnati in Cincinnati, Ohio. I'm happy to be here.
Dr Nevel: Wonderful. Well, I'm really excited to talk to you about your article today on this very interesting and unique set of movement disorders. So, before we get into your article a little bit more, I think just kind of the set the stage for the discussion so that we're all on the same page. Could you start us off with some definitions? What are paroxysmal movement disorders? And generally, how do we start to kind of categorize these in our minds?
Dr Mahajan: So, the term paroxysmal movement disorders refers to a group of highly heterogeneous disorders. These may present with attacks of involuntary movements, commonly a combination of dystonia and chorea, or ataxia, or both. These movements are typically without loss of consciousness and may follow, may follow, so with or without known triggers. In terms of the classification, these have been classified in a number of ways. Classically, these have been classified based on the trigger. So, if the paroxysmal movement disorder follows activity, these are called kinesigenic, paroxysmal, kinesigenic dyskinesia. If they are not followed by activity, they're called non kinesigenic dyskinesia and then if they've followed prolonged activity or exercise they're called paroxysmal exercise induced dyskinesia.
There's a separate but related group of protogynous movement disorders called episodic attacks here that can have their own triggers. Initially this was the classification that was said. Subsequent classifications have placed their focus on the ideology of these attacks that could be familiar or acquired and of course understanding of familiar or genetic causes of paroxysmal movement disorders keeps on expanding and so on and so forth. And more recently, response to pharmacotherapy and specific clinical features have also been introduced into the classification.
Dr Nevel: Great, thank you for that. Can you share with us what you think is the most important takeaway from your article for the practicing neurologist?
Dr Mahajan: Absolutely. I think it's important to recognize that everything that looks and sounds bizarre should not be dismissed as malingering. Such hyperkinetic and again in quotations, “bizarre movements”. They may appear functional to the untrained eye or the lazy eye. These movements can be diagnosed. Paroxysmal movement disorders can be diagnosed with a good clinical history and exam and may be treated with a lot of success with medications that are readily available and cheap. So, you can actually make a huge amount of difference to your patients’ lives by practicing old-school neurology.
Dr Nevel: That's great, thank you so much for that. I can imagine that scenario does come up where somebody is thought to have a functional neurological disorder but really has a proximal movement disorder. You mentioned that in your article, how it's important to distinguish between these two, how there can be similarities at times. Do you mind giving us a little bit more in terms of how do we differentiate between functional neurologic disorder and paroxysmal movement disorder?
Dr Mahajan: So clinical differentiation of functional neurological disorder from paroxysmal movement disorders, of course it's really important as a management is completely different, but it can be quite challenging. There's certainly an overlap. So, there can be an overlap with presentation, with phenomenology. Paroxysmal nature is common to both of them. In addition, FND and PMD's may commonly share triggers, whether they are movement, physical exercise. Other triggers include emotional stimuli, even touch or auditory stimuli. What makes it even more challenging is that FND’s may coexist with other neurological disorders, including paroxysmal movement disorders. However, there are certain specific phenom phenotypic differences that have been reported. So specific presentations, for example the paroxysms may look different. Each paroxysm may look different in functional neurological disorders, specific phenotypes like paroxysmal akinesia. So, these are long duration episodes with eyes closed. Certain kinds of paroxysmal hyperkinesia with ataxia and dystonia have been reported. Of course. More commonly we see PNES of paroxysmal nonepileptic spells or seizures that may be considered paroxysmal movement disorders but represent completely different etiology which is FND. Within the world of movement disorders, functional jerks may resemble propiospinal myoclonus which is a completely different entity. Overall, there are certain things that help separate functional movement disorders from paroxysmal movement disorders, such as an acute onset variable and inconsistent phenomenology. They can be suggestibility, distractibility, entrainment, the use of an EMG may show a B-potential (Bereitschaftspotential) preceding the movement in patients with FND. So, all of these cues are really helpful.
Dr Nevel: Great, thanks. When you're seeing a patient who's reporting to these paroxysmal uncontrollable movements, what kind of features of their story really tips you off that this might be a proximal movement disorder?
Dr Mahajan: Often these patients have been diagnosed with functional neurological disorders and they come to us. But for me, whenever the patient and or the family talk about episodic movements, I think about these. Honestly, we must be aware that there is a possibility that the movements that the patients are reporting that you may not see in clinic. Maybe there are obvious movement disorders. Specifically, there's certain clues that you should always ask for in the history, for example, ask for the age of onset, a description of movements. Patients typically have videos or families have videos. You may not be able to see them in clinic. The regularity of frequency of these movements, how long the attacks are, is there any family history of or not? On the basis of triggers, whether, as I mentioned before, do these follow exercise? Prolonged exercise? Or neither of the above? What is the presentation in between attacks, which I think is a very important clinical clue. Your examination may be limited to videos, but it's important not just to examine the video which represents the patient during an attack, but in between attacks. That is important. And of course, I suspect we'll get to the treatment, but the treatment can follow just this part, the history and physical exam. It may be refined with further testing, including genetic testing.
Dr Nevel: Great. On the note of genetic testing, when you do suspect a diagnosis of paroxysmal movement disorder, what are some key points for the provider to be aware of about genetic testing? How do we go about that? I know that there are lots of different options for genetic testing and it gets complicated. What do you suggest?
Dr Mahajan: Traditionally, things were a little bit easier, right, because we had a couple of genes that have been associated with the robust movement disorders. So, genetic testing included single gene testing, testing for PRRT2 followed by SLC2A. And if these were negative, you said, well, this is not a genetic ideology for paroxysmal movement disorders. Of course, with time that has changed. There's an increase in known genes and variants. There is increased genetic entropy. So, the same genetic mutation may present with many phenotypes and different genetic mutations may present with the similar phenotype. Single gene testing is not a high yield approach. Overall genetic investigations for paroxysmal movement disorders use next generation sequencing or whole exome sequence panels which allow for sequencing of multiple genes simultaneously. The reported diagnostic yield with let's say next generation sequencing is around 35 to 50 percent. Specific labs at centers have developed their own panels which may improve the yield of course. In children, microarray may be considered, especially the presentation includes epilepsy or intellectual disability because copy number variations may not be detected by a whole exome sequencing or next generation sequencing. Overall, I will tell you that I'm certainly not an expert in genetics, so whenever you're considering genetic testing, if possible, please utilize the expertise of a genetic counsellor. Families want to know, especially as an understanding of the molecular underpinnings and knowledge about associated mutations or variations keeps on expanding. We need to incorporate their expertise. A variant of unknown significance, which is quite a common result with genetic testing, may not be a variant of unknown significance next year may be reclassified as pathogenic. So, this is extremely important.
Dr Nevel: Yeah. That's such a good point. Thank you. And you just mentioned that there are some genetic mutations that can lead to multiple different phenotypes. Seemingly similar phenotypes can be associated with various genetic mutations. What's our understanding of that? Do we have an understanding of that? Why there is this seeming disconnect at times between the specific genetic mutation and the phenotype?
Dr Mahajan: That is a tough question to answer for all paroxysmal movement disorders because the answer may be specific to a specific mutation. I think a great example is the CACNA1A mutation. It is a common cause of episodic ataxia type 2. Depending on when the patient presents, you can have a whole gamut of clinical presentations. So, if the patient is 1 year old, the patient can present with epileptic encephalopathy. Two to 5 years, it can be benign paroxysmal torticollis of infancy. Five to 10 years, can present with learning difficulties with absence epilepsy and then of course later, greater than 10 years, with episodic ataxia (type) 2 hemiplegic migraine and then a presentation with progressive ataxia and hemiplegic migraines has also been reported. So not just episodic progressive form of ataxia has also been reported. I think overall these disorders are very rare. They are even more infrequently diagnosed than their prevalence. As such, the point that different genetic mutations present with different phenotypes, or the same genetic mutation I may present with different phenotypes could also represent this part. Understanding of the clinical presentation is really incomplete and forever growing. There's a new case report or case series every other month, which makes this a little bit challenging, but that's all the more reason for learning about them and for constant vigilance for patients who show up to our clinic.
Dr Nevel: Yeah, absolutely. What is our current understanding of the associated pathophysiology of these conditions and the pathophysiology relating to the genetics? And then how does that relate to the treatment of these conditions?
Dr Mahajan: So, a number of different disease mechanisms have been proposed. Traditionally, these were all thought to be ion channelopathies, but a number of different processes have been proposed now. So, depending on the genetic mutation that you talk about. So certain mutations can involve ion channels such as CACMA1A, ATP1A3. It can involve solute carriers, synaptic vesicle fusion, energy metabolism such as ECHS1, synthesis of neurotransmitters such as GCH1. So, there are multiple processes that may be involved. I think overall for the practicing clinician such as me, I think there is a greater need for us to understand the underlying genetics and associated phenotypes and the molecular mechanisms specifically because these can actually influence treatment decisions, right? So, you mentioned that specific genetic testing understanding of the underlying molecular mechanism can influence specific treatments. As an example, a patient presenting with proximal nocturnal dyskinesia with mutation in the ADCY5 gene may respond beautifully to caffeine. Other examples if you have SLC2A1, so gluc-1 (glucose transporter type 1) mutation, a ketogenic diet may work really well. If you have PDHA1 mutation that may respond to thiamine and so on and so forth. There are certain patients where paroxysmal movement disorders are highly disabling and you may consider deep brain stimulation. That's another reason why it may be important to understand genetic mutations because there is literature on response to DBS with certain mutations versus others. Helps like counselling for patients and families, and of course introduces time, effort, and money spent in additional testing.
Dr Nevel: Other than genetic testing, what other diagnostic work up do you consider when you're evaluating patients with a suspected paroxysmal movement disorder? Are there specific things in the history or on exam that would prompt you to do certain testing to look for perhaps other things in your differential when you're first evaluating a patient?
Dr Mahajan: In this article, I provide a flow chart that helps me assess these patients as well. I think overall the history taking and neurological exam outside of these paroxysms is really important. So, the clinical exam in between these episodic events, for example, for history, specific examples include, well, when do these paroxysms happen? Do they happen or are they precipitated with meals that might indicate that there's something to do with glucose metabolism? Do they follow exercise? So, a specific example is in Moyamoya disease, they can be limb shaking that follows exercise. So, which gives you a clue to what the etiology could be. Of course, family history is important, but again, talking about the exam in between episodes, you know, this is actually a great point because out– we've talked about genetics, we've talked about idiopathic paroxysmal movement disorders, –but a number of these disorders are because of acquired causes. Well, of course it's important because acquired causes such as autoimmune causes, so multiple sclerosis, ADEM, lupus, LGI1, all of these NMDAR, I mentioned Moyamoya disease and metabolic causes. Of course, you can consider FND as under-acquired as well. But all of these causes have very different treatments and they have very different prognosis. So, I think it's extremely important for us to look into the history with a fine comb and then examine these patients in between these episodes and keep our mind open about acquired causes as well.
Dr Nevel: When you evaluate these patients, are you routinely ordering vascular imaging and autoimmune kind of serologies and things like that to evaluate for these other acquired causes or it does it really just depend on the clinical presentation of the patient?
Dr Mahajan: It mostly depends on the clinical presentation. I mean, if the exam is let's say completely normal, there are no other risk factors in a thirty year old, then you know, with a normal exam, normal history, no other risk factors. I may not order an MRI of the brain. But if the patient is 55 or 60 (years) with vascular risk factors, then you have to be mindful that this could be a TIA. If the patient has let's say in the 30s and in between these episodes too has basically has a sequel of these paroxysms, then you may want to consider autoimmune. I think the understanding of paraneoplastic, even autoimmune disorders, is expanding as well. So, you know the pattern matters. So, if all of this is subacute started a few months ago, then I have a low threshold for ordering testing for autoimmune and paraneoplastic ideology is simply because it makes such a huge difference in terms of how you approach the treatment and the long-term prognosis.
Dr Nevel: Yeah, absolutely. What do you find most challenging about the management of patients with paroxysmal movement disorders? And then also what is most rewarding?
Dr Mahajan: I think the answer to both those questions is, is the same. The first thing is there's so much advancement in what we know and how we understand these disorders so regularly that it's really hard to keep on track. Even for this article, it took me a few months to write this article, and between the time and I started and when I ended, there were new papers to include new case reports, case series, right? So, these are rare disorders. So most of our understanding for these disorders comes from case reports and case series, and it's in a constant state of advancement. I think that is the most challenging part, but it's also the most interesting part as well. I think the challenging and interesting part is the heterogeneity of presentation as well. These can involve just one part of your body, your entire body can present with paroxysmal events, with multiple different phenomenologies and they might change over time. So overall, it's highly rewarding to diagnose such patients in clinic. As I said before, you can make a sizeable difference with the medication which is usually inexpensive, which is obviously a great point to mention these days in our health system. But with anti-seizure drugs, you can put the right diagnosis, you can make a huge difference. I just wanted to make a point that this is not minimizing in any way the validity or the importance of diagnosing patients with functional neurological disorders correctly. Both of them are as organic. The importance is the treatment is completely different. So, if you're diagnosing somebody with FND and they do have FND and they get cognitive behavioral therapy and they get better, that's fantastic. But if somebody has paroxysmal movement disorders and they undergo cognitive behavioral therapy and they're not doing well, that doesn't help anybody.
Dr Nevel: One hundred percent. As providers, obviously we all want to help our patients and having the correct diagnosis, you know, is the first step. What is most interesting to you about paroxysmal movement disorders?
Dr Mahajan: So outside of the above, there are some unanswered questions that I find very interesting. Specifically, the overlap with epilepsy is very interesting, including shared genes, the episodic nature, presence of triggers, therapeutic response to anti-seizure drugs. All of this I think deserves further study. In the clinic, you may find that epilepsy and prognosis for movement disorders may occur in the same individual or in a family. Episodic ataxia has been associated with seizures. Traditionally this dichotomy of an ictal focus. If it's cortical then it's epilepsy, if it's subcortical then it's prognosis for movement disorders. This is thought to be overly simplistic. There can be co-occurrence of seizures and paroxysmal movement disorders in the same patient and that has led to this continuum between these two that has been proposed. This is something that needs to be looked into in more detail. Our colleagues in Epilepsy may scoff this, but there's concept of basal ganglia epilepsy manifesting as paroxysmal movement disorders was proposed in the past. And there was this case report that was published out of Italy where there was ictal discharge from the supplementary sensory motor cortex with a concomitant discharge from the ipsilateral coordinate nucleus in a patient with paroxysmal kinesigenic cardioarthidosis. So again, you know, basal ganglia epilepsy, no matter what you call it, the idea is that there is a clear overlap between these two conditions. And I think that is fascinating.
Dr Nevel: Really interesting stuff. Well, thank you so much for chatting with me today.
Dr Mahajan: Thank you, Kait. And thank you to the Continuum for inviting me to write this article and for this chance to speak about it. I'm excited about how it turned out, and I hope readers enjoy it as well.
Dr Nevel: Today again, I've been interviewing doctor Abhi Mahajan about his article on diagnosis and management of paroxysmal movement disorders, which appears in the August 2025 Continuum issue on movement disorders. I encourage all of our listeners to be sure to check out the Continuum Audio episodes from this and other issues. As always, please read the Continuum articles where you can find a lot more information than what we were able to cover in our discussion today. And thank you for our listeners for joining today. And thank you, Abhi, so much for sharing your knowledge with us today.
Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.