The Podcast focuses on pressing issues surrounding environmental exposures related to neurodegenerative diseases, particularly Parkinson's disease, and the current state of advocacy and regulation within Australia. A narrator opens the discussion by revealing their childhood experience on a farm in Orange, which sets the stage for a deeper exploration of the impact of agricultural chemicals. The conversation highlights the lack of progress in Australia regarding the regulation of environmental toxins, despite ongoing advocacy efforts from colleagues in Western Australia. It becomes clear that the Australian Pesticides and Veterinary Medicines Authority (APVMA), responsible for overseeing these chemicals, operates with significant gaps in surveillance and accountability, relying on self-reported data from the chemical companies themselves.

As the discussion unfolds, the narrative outlines the severe consequences that arise from the unrestricted use of long-lasting agricultural chemicals, including their potential link to an increase in Parkinson's cases, particularly in areas like Orange. The speaker elaborates on alarming trends, noting that patients diagnosed with Parkinson's are increasingly younger and may possess genetic susceptibilities that complicate the understanding of the disease's etiology. The regulatory framework is critiqued for a lack of oversight and actionable measures to protect public health, which further reiterates the urgent need for advocacy in this sector.

Transitioning into the topic of animal models in Parkinson's research, the speaker reflects on the limitations of existing models to accurately replicate human disease, emphasizing the difficulty in reproducing the pathophysiological characteristics of Parkinson's in laboratory conditions. The discussion touches on specific historical cases that have contributed to our understanding of the disease but ultimately stresses the inadequacy of current animal models.

The conversation then shifts to practical clinical considerations related to patients suffering from dysphagia — swallowing difficulties that often accompany Parkinson's disease. The speakers share insights on assessment approaches, emphasizing the importance of quantifying swallowing function against normative data and implementing environmental adjustments to improve patient outcomes. Methods such as instrumental swallowing assessments are discussed, revealing challenges in accessibility to diagnostic services and the shift toward innovative solutions, including fibroptic endoscopic evaluation by trained speech pathologists.

The lecture proceeds to touch on nerve conduction studies, particularly addressing common conditions such as carpal tunnel syndrome. The necessity of these investigations is highlighted, along with their relevance to guiding treatment decisions. The importance of precise referrals for neurophysiological testing illustrates the intricate balance between clinical intuition and empirical evaluation.

Further discussion introduces advanced therapeutic options for Parkinson's patients, such as deep brain stimulation (DBS) and continuous medication delivery systems like Duodopa and apomorphine. Patient selection for such interventions is emphasized as a critical factor, as not all individuals will derive benefits from these advanced treatments. Considerations surrounding patient health, age, and the presence of coexisting conditions are outlined to underscore the complexity surrounding these decisions.

The session concludes with an acknowledgment of the student-run speech pathology clinic available to patients, highlighting its role in improving accessibility to vital services for those impacted by MND and Parkinson's. The collaborative environment fosters learning opportunities for students while ensuring quality patient care. Overall, the lecture underscores the urgent need for regulatory reform, the importance of innovative clinical approaches, and the continuous evolution of treatment strategies to better address the challenges faced by patients with neurodegenerative diseases.

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Dom, I guess it's now that I should declare that I actually grew up in Orange

and lived on a farm for a period of time as a child. So I'm feeling a little

anxious about your comments about environmental exposure in Parkinson's.

So one of our audience members asked a question about advocacy for trying to

remove some of these environmental exposures in Australia.

There's one of our colleagues in Western Australia who's strongly advocating

for this. Is there any progress in this area? Where are we up to?

No, there's no progress in Australia at all.

The APVMA, which is in Armidale, is the regulatory body that is responsible

for approving and importing the millions of kilograms of environmental poisons

that are in our food chain each year.

The APVMA reports to the Department of Agriculture.

So that's like the fox in charge of the hen house.

The safety data on the chemicals that come into our food chain are provided

by the chemical companies that make the chemicals.

There's no post-marketing surveillance. The Morrison government disbanded the

surveillance unit to look at chemical residuals in the domestic food market

in Australia. So food is labelled for export.

There is some requirement for producers to document what chemicals they've used

at what rate and how close to harvest.

But there's no interrogation of the self-reporting facility.

So it's a complete abrogation of responsibility. Most of these chemicals are

incredibly long-lived.

They work in agriculture.

By killing cells, whether they're fungal cells, as fungicides,

or plant cells as herbicides, or the nervous system of insects as insecticides.

So, hardly surprisingly, there is blowback.

There is no requirement. So I run a farm in Hunter Valley.

I can go and buy a 1,000-litre IBC of any chemical that I want from Nutrients

Agricore or Farmer's Warehouse.

And after I drive it off the lot, there's no requirement for me to report to

anyone about how I use it, at what rate.

There's no disposal system apart from, you know, There's an internet-based system

that you're supposed to do as part of your training so that you run a farm,

but there's no interrogation of that.

So you would have seen the blueberry farms up around Lismore,

a chemist,

industrial chemist, interrogated systematic pesticides and insecticides and

herbicides in random blueberries that she bought from the supermarket,

just last month it was reported,

and she found traces using mass

spec of chemicals that were banned in Australia more than 20 years ago.

So, orange has a much higher frequency of Parkinson's disease.

The case acetaminate of Parkinson's disease is not as good as,

say, for example, motor neurone disease, where using mortality data,

because motor neurone disease is uniformly fatal,

in the last 37 years, motor neurone disease has tripled the,

in Australia as a cause of death and that's

not genetic motor neurone disease so in

according the weeds in the research in Parkinson's disease

so I've been you know my PhD was

in Parkinson's pathogenesis and the genetics and

genetic susceptibility has dominated the the architecture just like in motor

neurone disease of what's going on because that you know benchtop scientists

can and manipulate and control genetic models of disease much more than environmental.

So our Parkinson's patients are getting younger.

We interrogate for genetic causes all the time, but we have multiple kindreds

with autosomal dominant, parent-to-child Parkinson's disease,

and we don't find a genetic cause.

So there may well be genetic susceptibility in terms of detoxification enzymes

and other repair mechanisms, but it is, from sitting where I sit,

it's a tidal wave and the regulators don't care.

Yeah, it's a massive challenge, isn't it, and some of those numbers are frightening

with the dramatic increases in incidents of both Parkinson's and motor neurone disease.

Or do animals exhibit Parkinson's symptoms?

Yeah, great question. In fact, I mentioned Arvid Carlson as the first person

who identified dopamine deficit.

So they did that by using a chemical called reserpine to deplete dopamine from the brains of rodents.

The human primate motor system is pretty unique.

So there aren't really that many valid animal models for human Parkinson's disease.

They're often promoted. So there was a compound called MPTP that was cooked

up by a medical student in San Francisco who was making pethidine in his grandmother's basement.

And as you do on uni holidays, cook up pethidine.

And one of the contaminants was this chemical called MPTP, and that gets converted

into a thing called a methylpyridinium iron, and that is terribly toxic to your substantia nigra.

But pathologically, those patients, when they died, so he gave the pethidine

to a whole heap of his mates, and they all got this acute Parkinsonism.

But pathologically, it looks very different. So alpha-synuclein Lewy body positive

Parkinson's disease is very difficult to recreate in the laboratory.

So a lot of the animal modelling is acute single-hit toxic and not really that valid.

Is it possible to recreate Parkinsonism from a variety of organic and inorganic

compounds? Yep, you can.

But it isn't necessarily applicable to human Parkinson's disease.

Yeah. Sally, we might just switch gears now and talk a little bit about dysphagia.

So you mentioned obviously that when we think about dysphagia,

we're often thinking about thickened fluids.

Can you tell us a little bit more about what some of the kind of steps before

that look like? You know, what sort of swallow programs can we implement?

How much improvement or stabilization can we expect with some of our patients with PD?

Yeah okay thank you um i think

when we first see someone and we can see uh

mild changes to swallowing impairment and we

we measure swallow now with the numerical data so we

actually have baseline norms about how quick

people's swallowing is against age um and so we can quantify if it's disordered

in against an age match control um we we look at environmental behavioral management

strategies so we first off we control for the amount of food or fluid you put in your mouth,

you're going to do it better if it's less in there um

so really simplistic views to start with um when

we start to dance into texture modification and

i do it the most with fluids because water is

the hardest fluid to drink um we

look at well what's a naturally occurring slightly

thicker fluid and a naturally occurring slightly thicker fluid

is water with cordial in it you add a little bit more texture you make it a

little bit easier to swallow so sometimes we just do some mild adjustments um

there uh and then we we sometimes just sit back and go well what's the frequency

of dysphagia symptoms and are they really.

So abnormal that they're disrupting you, both in your health and your participation.

And sometimes it's not enough.

And if I did an instrumental swallow, I might see a worse swallow than what

I'm seeing behaviorally.

So sometimes we just go, let's just watch and also see how we're going.

So by instrumental swallow, I think this is one of the questions that came up. Yeah, right.

You mean the modified barium swallow, those sorts of things?

Yeah, we have modified barium swallow has had a name change in recent times.

It's called Video Fluoroscopic Study of Swallow.

They're hard to get as an outpatient in New South Wales through Sydney hospitals.

They're really hard to get.

You can go to Concord Hospital to their clinic that does it,

but Concord's not really accessible to everyone. So that might not be the best option.

What is emerging now is that speech pathologists are being trained in the use

of fibroptych endoscopic evaluation of swallowing.

And we are here at Macquarie University in the speech and hearing clinic where

we will pop down a camera and actually look at someone's swallow in real time.

Of course, it's only a real-time snapshot of their swallow in that moment of

time with a very small amount of food or fluid, but it gives us a bit of an

idea of what's happening.

That's probably the most accessible way of doing it. So would that be something

you do at your first assessment?

We are with Parkinson's, only if the predominant feature of that Parkinson's

presentation is swallowing.

If it's a Parkinson's referral, which they typically are, we would do what we

call a bedside evaluation, which is literally just an observational evaluation

of someone swallowing together with speech measures.

Because that gives us a bit of an impression generally about someone's swallow

efficiency without watching them swallow under instrumental conditions.

Great, thank you. Changing gears again, Candice, so you gave us a terrific overview of,

some of the pathophysiological processes, you know, with neuronal or peripheral

nerve injury and those sorts of things.

I guess thinking about GP referrals and things, what are the most common reasons

patients are sent for nerve conduction studies?

When should the audience be thinking about sending patients along for tests?

I think the most common reason would probably be when you suspect carpal tunnel syndrome.

But any patients with, I guess, possible cervical radiculopathy or peripheral

neuropathy, someone who has numbness in both feet and there is no clear reason,

would be also very common.

Now, I mean, it's very broad because we can do electromyography also without

doing nerve conduction studies.

So if someone has some weakness and you're concerned that there might be a muscle

disorder, we can certainly look into that also.

And I guess the benefit of doing neurophysiological testing,

say for carpal tunnel syndrome, just thinking about why is it important, what's the benefit?

So that gives us an idea of the severity of the carpal tunnel syndrome,

which will help us decide on the best treatment for the patient.

So if we just see slowing of conduction velocity, we're not that worried.

But if the patient starts losing amplitude, if we start losing axons,

that's definitely a sign that that patient should be considered for surgery.

And now if you have enough conduction study in a patient where you barely can

get responses, which happens sometimes, or very severe carpal tunnel syndrome,

it's also important to know that.

Even if there is already lots of axonal loss, these patients might still benefit

from surgery because decompressing the nerve will usually help with the way it feels.

These patients are often in lots of discomfort or pain, and having the nerve

decompressed, even if it might not give a good functional recovery,

will usually help with more subjective symptoms.

Yeah, I'd add that it's helpful to do it before surgery too.

So often the surgeons will send a patient, oh, I did the surgery and they're not any better.

How can we compare? We don't know what they were like before the surgery.

So it can be very helpful both before and after surgery.

I think we've got a question from the audience. Look, I won't ask you about

deep brain stimulation.

What kind of patients will benefit? Because I've sent some patients to Stephen Tisch in St. Vincent.

Most of them he said yes, no. And then a younger guy, he's amazed how much improvement he has.

Is there any new treatments in Parkinson's therapy apart from medicine?

Like pharmacotherapy, bread and butter, we know to some degree,

something new that we want to know. That's what we would like you to do. Yeah.

And so subthalamic nucleus deep brain stimulation was developed in the early

1990s by a neurosurgeon in Marseille called Benebed. And everyone thought he was crazy.

Attacking the subthalamic nucleus. But in fact, it's a tremendous,

even though the subthalamic nucleus is not a dopaminergic nucleus, it's glutamatergic.

So it sort of stuns this bit deep inside the brain and it is a life-saving therapy.

So of my 800 patients with Parkinson's disease at the moment,

I have about 60 patients who've had ST and DBS.

So picking the right patient for this is really critical because the older the

patient it is, it is the higher the risk.

So it's very uncommon for the surgeons and the neurologists involved like Steve

and Paul Silberstein and the team at Westmead and then us here next year.

If you're over the age of 75, the risk of hemorrhagic complication or stroke

goes up quite dramatically because people's brains get stiffer,

and when you're putting big electrodes down into the brain,

the risk of pranging a blood vessel goes up.

The cost of the surgery is still very high, so Westmead does do a little bit

of publicly funded ST and DBS.

I think Vinny's does a little bit as well, but mostly out of pockets,

about 20 to 30,000 for the whole procedure, the surgery and the after surgery care.

The surgery mainly helps in people who are dyskinetic patients.

Patients who are having a lot of peak dose dyskinesia from the medicines and

preventing that dyskinesia is the real goal of therapy, of oral therapy.

But sometimes it just happens and that's when you look at looking at ST and DBS.

So when the oral therapies are not working or if you're having side effects

of the oral therapies that are causing problems.

So you heard me talk about impulse control disorders. so when the patients start

getting into troubles with those or with dopamine dysregulation.

If there's coexistent dementia, then you shouldn't be thinking about putting in DBS.

And you've got to look very carefully, and all the DBS teams look very carefully

for coincident cognitive disturbance and even major premorbid psychiatric disturbance.

So if there's a big psychiatric burden, because there is a risk of suicide in

the immediate post-operative period.

So patient selection, like all operations, patient selection is paramount.

Only really around about probably at most 5% of patients with Parkinson's disease

are appropriate for ST and DBS.

The other advanced therapies include Duodopa, which is putting in a duodenal.

Tube, so like a peg tube into the tummy, and you have a cassette of levodopa

that provides this constant stream of levodopa into your duodenum,

and that evens out the fluctuations.

There's been a lot of press around FOS levodopa, which is otherwise known as

Violev, and that's a subcutaneous form of levodopa that again is delivered by

a pump through a cassette, and it's very expensive to the PBS.

So it is approved and it is available

on PBS, but it is a big cost and not necessarily that advantageous.

People do need to be able to manage the catheters and the subcutaneous catheters.

There's another therapy called apomorphine, which you may have heard of,

and that's another very potent dopamine agonist, and that can be given by a pump system as well.

So the advanced therapies are

life-saving but need to be done by the people who are used to doing it.

Yeah, patient selection is really critical, not just DBS but some of these other

things as well, isn't it?

I think we've got an audience question over here. What is on-off phenomena and

is it dose-related and what do we do before differing?

Excellent. So as our dopamine neurons die, our ability to buffer levodopa gets less.

And so the on-off phenomenon relates to crossing the threshold of having enough dopamine in your brain.

So if we think of dopamine in our brain as oil in an engine,

so even if you have a tank full of petrol and a supercharged engine,

if you don't have enough oil, your engine doesn't run.

So on-off phenomenon is your fluctuations in the oil in your engine,

and that can be either dose failure or sudden off,

or the first thing that we see is this thing called wearing off,

whereas instead of the normal four to five hours from each dose of levodopa,

we see patients looking for their next dose and they have to bring it forward.

So, yeah, again, that's very gender-based and weight-based, the approaches to on-off phenomenon.

And it occurs with increasing frequency the longer that you've had your Parkinson's disease.

So, coming back to Candice, we've had a question about the distribution of sensory

symptoms in carpal tunnel syndrome.

So, I think most of us know that people can have tingling in the hands.

You know, what do you think about patients who have tingling that's mainly affecting

the fourth and fifth digits?

Can we see that in carpal tunnel?

You know, should we be thinking about ulnar neuropathy? Is that something we

can investigate as well?

What do you think about that? And the first thing to say is often patients struggle

to say exactly where it is numb or tingling.

Like they wake up, the whole hand seems to be tingling.

But the median distribution is the first three and a half of the ring finger,

and the ulnar distribution is the rest.

So we can definitely assess any sensory nerves, especially median ulnar and

radial. This is quite straightforward to do that.

And that will give us a good idea of what's exactly going on when the patient

struggles to describe what they feel.

Yeah, so I mean, it's a standard protocol when you're doing a carpal tunnel

study, you'll assess the median nerve, that's the main event,

but you'll also look at the ulnar nerve.

And so we can make that distinction. I think, just to agree,

you know, it can be really hard to tell sometimes.

The benefit of clinical neurophysiology is that it's an extension of the history

and examination. So if we're not sure on the history and exam,

often the nerve conduction studies will give us the answer.

So that's really helpful. Thank you.

Sally, I guess we know that Dominic leads a very big and busy MND clinic here,

and you've been involved with that as well as assessing patients with Parkinson's.

Obviously, you showed us the website and you can find a speech pathologist anywhere

in Sydney, et cetera. But, you know, what sort of services do we offer here?

You know, if we've got patients that are, you know, have MND,

have Parkinson's, how do they become engaged with your service?

Yeah, so they can actually, so I sit in a, it's called the Australian Hearing Hub.

It's in the main faculty of the university and it's where audiology,

psychology and speech and hearing sciences sits. And we have a clinic in that building.

It is actually a student-run clinic. So my other dual role here is clinical

educator of speech pathology students who are master's students.

So that does afford a little bit of a financial discount to clients if they

are accessing that service.

But they still have a speech pathologist in the room. So they're not being left sort of unsupervised.

So we have that service. we provide so I accept referrals from.

Any adult and any adult is actually anyone over age of 16 by broad definition

and I would see them in a clinic predominantly for an assessment but I do do a lot of home visits.

I set up a lot of assistive technology in the community for people with MND

or people who have mobility disruptions associated with whatever clinical diagnosis

that have that prevents them from walking in my door and I go to them and see them in their home.

So, they don't need a GP referral. They can make a referral.

There is an intake process.

There is a waiting list. I am not the only speech pathologist on site either.

So, they don't necessarily need to see me. I have other colleagues in that department

and we would follow that through in that environment.

Thank you. I think it's brilliant to have student speech pathologists involved with the service.

Obviously, it's great for their learning, but anything that can make this incredibly

important service more accessible, I think, is really, really valued and, you know, fantastic.

So, I think we've come to the end of the session. It's, I guess,

just up to me now to thank our speakers once again for a very stimulating and

interesting session, both the Q&A and the talk. So, thanks very much.