NeuroVoices: A. Jon Stoessl, MD, on Understanding Plasticity and Disease Trajectory in Parkinson Disease | NeurologyLive

Parkinson illness (PD) is a relentlessly progressive neurodegenerative dysfunction. The breakdown of compensatory mechanisms that affect putaminal dopamine processing could contribute to the development of motor signs. In a beforehand revealed research, investigators analyzed a cohort of 78 people with sporadic PD and 35 wholesome controls utilizing multitracer positron emission tomography to look at the evolution of adaptive mechanisms affecting striatal dopamine processing over the course of illness development. The findings from the research, performed by senior writer A. Jon Stoessl, MD, and colleagues, indicated that compensatory mechanisms diminish as PD advances.¹

Through this analysis and different research, Stoessl has earned recognition as a number one neuroscientist whose work has vastly superior the understanding and therapy of motion issues. In acknowledgment of his contributions, he was named the recipient of the C. David Marsden Award Lectureship on the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii. The honor acknowledges Stoessl’s distinctive analysis elucidating the neurobiology of motion issues and his efforts to translate these discoveries into significant scientific functions.²

In a brand new iteration of NeuroVoices, Stoessl, neurologist at University of British Columbia and editor-in-chief of Movement Disorders, reviewed his analysis on compensatory mechanisms within the PD mind, specializing in how anatomical and practical segregation in wholesome people breaks down in sufferers with PD. He emphasised the function of the striatum in somatotopic illustration and the potential for life-style interventions, similar to train, to affect irregular plasticity. Stoessl additionally mentioned the variability in illness trajectory amongst sufferers, underscoring the worth of understanding why some people preserve higher operate over time.

NeurologyLive: Could you summarize your lecture and share the important thing takeaways you had been making an attempt to convey?

A. Jon Stoessl, MD: We’re actually , and have been for a few years, in compensatory mechanisms within the mind in PD. Why do some folks do higher than others, and what diploma of plasticity is that accessible to the mind? The newest factor that I talked about it this, we all know that the mind is organized in order that totally different anatomical areas of the physique are represented in sure locations, and that features the striatum. Also, totally different capabilities are represented in parallel loops like motor, which everyone thinks about, but additionally cognitive operate and reward operate.

It’s at all times been assumed that these anatomical and practical separations are segregated in the way in which they’re represented within the mind, however no person has actually checked out this in PD per se. We got down to do research to take a look at dopamine launch in response to numerous stimuli, each totally different elements of the anatomy, hand versus foot, but additionally motor versus cognition versus reward.

To sum it up, we discovered that whereas these items are separated in sufferers with out PD, in wholesome people. In PD, that separation breaks down. The implications could also be many. First, the actual fact that you’ve this segregation implies that an vital a part of the method isn’t a lot within the substantia nigra, the place the dopamine cells originate, however reasonably within the striatum, the place they’re projecting to as a result of it is the striatum the place there’s this so-called somatotopic illustration.

In addition, when you consider it, when you compensate for motor impairment by activating cognitive or reward facilities within the mind, what occurs when it’s a must to do each? We know that in sufferers with PD, issues break down after they try to multitask.

Over the previous a number of years, there’s been a number of dialogue in neurology about reimagining the continuum of illness and what the circumstances are, how does your work inform that pondering in PD?

You’re referring to one other subject, a highly regarded subject proper now. How will we outline illness? Historically, we have executed this on scientific grounds, and there’s now an growing curiosity in organic markers, which may embrace fluid markers or the seeding amplification assay to establish misfolded alpha-synuclein. But it may well additionally embrace neuroimaging markers to search for proof of denervation.

I might say that is an unresolved subject, with fairly strongly held opinions on a number of sides, as a result of most of us are clinicians, and so we discover it tough to push apart the concept of taking the scientific manifestations under consideration. But additionally, there are big moral points. If you’ve anyone who’s received nothing however a genetic predisposition or an irregular lab check, do you actually pull them right into a room and say, “Guess what? You’ve got this disease,” particularly when you do not actually have a therapy to supply them?

This is all related to our work in some methods, in that we’re seeking to see whether or not life-style interventions can have an effect on the irregular plasticity, on the irregular wiring. If you could possibly deal with that with like train, then you could possibly truly have an effect on the course of the illness. It additionally in all probability has implications when it comes to understanding the trajectory of the illness and why some sufferers are fairly profitable with their illness, if you’ll.

Over a profession, seeing 1000’s of sufferers with PD, no 2 are precisely alike. Why is it that some sufferers do remarkably properly, whereas others undergo a really tough time? In basic, understanding why some folks do properly with illness could find yourself being extra informative than all of the adverse elements. It’s an effective way of understanding what it’s that occurs, as a result of we do have both intrinsic or extrinsic defenses and so to higher admire these may have a big effect.

When it involves your profession, how vital is it to return to a spot like MDS and gather a number of data out of your colleagues to assist inform how one can present higher care?

The society holds a particular place in my coronary heart. I joined the 12 months the society began, and I’m a co-author on a paper within the very first subject of Movement Disorders. But extra to the purpose, I’m surrounded by fantastic colleagues. I work every day with fantastic colleagues. I’ve held a lot of roles within the society, the latest of which is as editor of the journal. That’s been an infinite privilege. It’s an ideal duty, however I get to work with the most effective folks on this planet, and I get to see what’s taking place earlier than it is truly on the market.

From your scientific perspective, what stood out to you as a spotlight at MDS 2025?

I believe in all probability a greater understanding of the alternative ways during which folks can get PD and the way the trajectory can differ between people. From a care perspective, I believe a greater understanding of the way to deal with irregular plasticity can be 1 instance. There are nonpharmaceutical approaches to therapy, which isn’t in any strategy to denigrate the pharmaceutical approaches. It’s an extremely vital a part of improvement, which may solely happen within the face of a greater understanding of the mechanisms that contribute to illness.

That’s why the mixing of fundamental science and scientific exercise is so vital. In reality, my very own work, which I’ve executed along side a physicist with whom I’ve labored for practically 30 years, couldn’t have been executed with out these multi- and interdisciplinary approaches.

Transcript edited for readability. Click right here for extra protection of MDS 2025.

REFERENCES
1. Nandhagopal R, Kuramoto L, Schulzer M, et al. Longitudinal evolution of compensatory modifications in striatal dopamine processing in Parkinson’s illness. Brain. 2011;134(Pt 11):3290-3298. doi:10.1093/mind/awr233
2. Stoessl J. C. David Marsden Lecture Award: Functional Reorganization and Compensation in Parkinson’s Disease. Presented at: 2025 MDS Congress; October 5-9; Honolulu, Hawaii. Presidential Lectures.