Dystonia, A Disorder Longing for More Therapies

November 2, 2018

The Pediatric Movement Disorders Neurologist at UT Southwestern recommends that when encountering a patient with a movement disorder to organize your thought process in 3 steps.

Jeff Waugh, MD, PhD

At the 47th Child Neurology Society Annual Meeting in Chicago, Illinois, NeurologyLive sat down with Jeff Waugh, MD, PhD, Pediatric Movement Disorders Neurologist, University of Texas Southwestern, Dallas, to dive deeper into his presentation on inherited dystonias, a movement disorder that is in great need of new and effective therapies.

Specifically, Waugh noted the limitation of deep brain stimulation in this patient population and that the identification of multiple stimulation sites would be a huge step forward for dystonia therapy. Additionally, the knowledge prior to surgery of the patient’s response and if they were likely to respond well or not would also be helpful for not only patients but also clinicians.

When encountering a patient with a movement disorder, Waugh suggests that clinicians organize their thought process in 3 steps to avoid whole exome or other broad genetic approaches: nail down the phenomenology of movement, a bedrock principle; then step back and look again to see if there are other movements that are not well explained by the primary movement phenomenology; and finally, look at other characteristics like age at onset, the site of onset, the rate of progression, any temporal features that gets you to a much narrower differential. This approach should then allow clinicians to work through a diagnostic approach, with imaging, if need be, limited genetic testing, if need be, medication trials both as a therapeutic and diagnostic approach.

NeurologyLive: Can you provide a brief overview of your presentation?

Jeff Waugh, MD, PhD: My presentation is on the inherited movements disorders, which are a pretty broad category that incudes both primary movement disorders, when you have the disorder alone, and degenerative disorders that lead to a series of changes, encephalopathy, movement disorders, spasticity, etc. We’re doing a 3-part series, one on paroxysmal disorders, one on chorea and I’ll be speaking on dystonia.

Dystonia in childhood is about 90% secondary, following brain injury from things like stroke or cerebral palsy, 10% are inherited. Within that 10% there is a huge range of age at onset, severity, pattern of spread and overlap of different movement disorders. We’ll be speaking on the genetic background that predispose kids to these movement disorders, and laying out a framework for how to characterize abnormal movements.

The inherited dystonias can come as primary, a category where you have only dystonia, or dystonia plus, where you have dystonia-plus other movement disorders such as myoclonus or chorea. That dystonia-plus touches on the presentations of my co-presenters, several syndromes can fall into the dyskinesia category with dystonia, chorea or myoclonus, or into the severe chorea category like GNAO1 or ADCY5, in which you have dystonia as a secondary feature and chorea as the primary feature.

We have only a few treatments for movement disorders. We have a few medications, such as dopamine supplementation, anticholinergics like Artane. The mainstays of treatment at most academic medical centers have become Botox injections and treatment with deep brain stimulation, which of course are invasive and in many cases require the surgical options.

What’s your advice for clinicians treating this patient population?

JW: I suggest that when you encounter a patient with a movement disorder you organize your thought process in 3 steps. First, you really nail down the phenomenology of movement, get in the right movement category. If you are thinking it’s myoclonus and it’s actually dystonia or if you think it’s chorea and it’s actually a tic, you’ll never get to the right list of genes to send or the right list of medications to try—so getting the phenomenology is really the bedrock principle.

Once you’ve got the dominant movement phenomenology down, then you take a step back and look again to see if there are other movements that are not well explained by the primary movement phenomenology. For example, in myoclonus dystonia the dystonia might catch your eye first, but the myoclonus as a background feature is a really important clue.

Once you’ve got the phenomenology nailed down, then you go on to the age at onset, the site of onset, the rate of progression, any temporal features like time of day predominance or associated things like exercise or triggers with certain foods, that gets you to a much narrower differential. Once you’ve nailed down the phenomenology, organize your thoughts about the timing, onset, etc., then you can work your way through a diagnostic approach, with imaging, if need be, limited genetic testing, if need be, medication trials both as a therapeutic and a diagnostic approach. Those 3 steps can get you to the right answer for the majority of patients, without having to go to whole exome or other really broad genetic approaches.

What additional questions remain unanswered?

JW: Well, the treatments we have for dystonia are few, so everyone who treats dystonia patients longs for more therapies. Deep brain stimulation is hugely helpful for some patients, but right now we’re limited to a single site, the globus pallidus interna (GPi), so stimulating sites other than the GPi or stimulating multiple sites would be a huge step forward for dystonia therapy. Being able to know, before a surgery, that a given patient was likely to respond well or not, would also be a very helpful step. Those are the research aims that my collogues and I are working on.

Anything else you want to mention?

JW: Movements disorders are unique in neurology in that you can do so much just with the casual observation, just sitting back and watching the patient can very often help you to the diagnosis without having to rely on EEG, MRI, or other expensive testing. It’s really appealing to be a movement disorder neurologist for those who are in resource-limiting settings. My colleagues in places in the world where they don’t have access to testing can still do a tremendous amount of movement disorders work because of the focus on clinical observation skills. That’s one of the things that makes it really fun.

Transcript edited for clarity.