So, it's my very great privilege and honour to introduce Professor Dominic Rowe.

I don't think Dominic needs a lot of introduction to this audience,

but Dominic is the inaugural Professor of Neurology here at Macquarie University,

and he has both clinical and research expertise in the fields of motor neuron disease,

Parkinson's disease, and other neurodegenerative diseases.

Today, he's going to give us an update on Parkinson's disease,

and I'll let you take it away, Dom. Thanks, James.

I've got 20 minutes to do Parkinson's disease, so this is going to be really quick.

What I thought I'd do first is to just put the Parkinson's disease in a historical context.

So in 1817, a surgeon in East London, in the Sound of Bowbells,

a true East Ender called James Parkinson,

described six patients, two of whom were his patients and four of whom he saw in the street.

And he described the constellation of symptoms that he codified as paralysis agitans.

So he called it paralysis agitans.

The father of modern neurology, Jean Charcot, read James Parkinson's tome,

and he coined the term Parkinson's disease.

It was until 100 years after Parkinson first described paralysis agitans that

a PhD student in Paris actually identified the pathologic substrate of Parkinson's

disease, a chap called Tritiakov,

who systematically went through the brains of patients with Parkinson's disease

and first identified that the substantia nigra was affected by Parkinson's.

The English and the Americans didn't believe it. It was the Swedish who made

the next huge leaps forward in Parkinson's disease.

And that was Arvid Carlson in the 50s and 60s, who was able to demonstrate that

it was a deficit in the major transmitter dopamine, as well as other transmitters.

So we falsely think of Parkinson's disease as just a dopaminergic deficit, but that's not all.

So Arvid Carlson actually after describing it in the 50s and 60s finally won

the Nobel Prize anyone know the year that he won the Nobel Prize for identifying dopamine deficit,

well you know good things come to all who wait the year 2000 was,

He got the Nobel Prize for Physiology and Medicine for identifying.

And Oli Hornikovic, who was a very famous Austrian pathologist and neurochemist

who described it at exactly the same time, was incredibly pissed off because

Carlson got the Nobel Prize and he didn't.

In 1965, George Kotsius, who was a resident working in New York City,

introduced levodopa as therapy.

So if it's a dopaminergic deficit, give people dopamine, they'll get better.

Well, dopamine doesn't cross the blood-brain barrier.

But George Kotsius worked out that if you gave a precursor of dopamine,

leave it OPA, that that crosses the blood-brain barrier. So it wasn't Oliver Sacks.

Wasn't him. It was George Kotsius in 1965, so the year I was born.

It's still the best therapy, levodopa.

So Merck Sharpen Dome introduced carbidopa, so carbidopa produces a thousand-to-one

gradient for levodopa to get into your brain.

And Roche produced benserazide about three years later, which is why most levodopa

therapy is in the form of levodopa, carbidopa,

90% and 10% because MSD got there first.

But however, Matapar has its place and I'll come to that.

So what are the clinical features of Parkinson's disease?

Well, there are more than 200 clinical features of Parkinson's disease and there

are no two patients who are the same.

There's a very long prodrome in Parkinson's disease.

REM sleep behavior disorder that Alice touched on. Hyposmia Constipation.

Vivid dreams, behavioral change, depression, anxiety, all in the premotor phase

of Parkinson's disease.

By the time you present with tremor, slowness or stiffness, you've lost 70%

of your brain's dopamine.

You've had the disease for 10 to 20 years.

Parkinson's disease is a whole-body disease. Skin changes, hair changes,

bone changes, vitamin D changes, hepatic changes, gut changes.

30% of people with Parkinson's disease never have tremor, ever.

So bradykinetic rigid Parkinson's disease often is diagnosed much later.

And there are quite a few mimics for Parkinson's disease. And it's important

to remember that other diseases like PSP, progressive supranuclear palsy,

which is characterized by early significant falls.

So if your patient looks Parkinsonian and they're falling in their first year,

then it might not be Parkinson's disease.

Multiple system atrophy has several different forms, but the most common of

which looks like Parkinson's disease, but it's a much worse disease.

Normal pressure hydrocephalus, and it's important to remember that some drugs,

notably valproate, epilim.

So perhaps once or twice a year, I have a patient who's sent to me with a diagnosis

of Parkinson's disease, and they've been on epilim, and you stop their epilim,

and their Parkinson's disease goes away.

And then there are other mimics that look like Parkinson's disease.

In fact, yesterday, one of my patients that I saw who's now in her 80s had been

told very confidently by the movement disorder clinic at Westmead 20 years ago,

and then by another very learned neurologist 10 years ago that she had Parkinson's

disease, and she doesn't.

She's got essential tremor. So we stopped all of her Parkinson's therapy,

put her on some beta blockers, and she can now do everything.

Parkinson's disease has doubled in our society since I started working as a junior doctor.

We have a very good idea of how many patients have Parkinson's disease from PBS data.

So in 1998, there were 60,000 Australians on dopamine replacement therapy for Parkinson's disease.

Now, that may be a little bit rubbery because sometimes people are on medicines

and they don't have Parkinson's disease. And sometimes people have Parkinson's

disease and they're not on therapy.

Last year, it's 130,000 Australians. Double.

Male to female, two to one. Two to one.

There is no accurate incidence or prevalence study of Parkinson's disease in Australia.

Parkinson's disease in Australia is very rarely genetic.

So, there are genetic causes of Parkinson's disease.

In the mid-1990s, alpha-synuclein genetic abnormalities were first identified

with mutations, duplications, triplications, and that causes autosomal dominant

Parkinson's disease, and it's pretty bad Parkinson's disease.

Subsequent to that, LRRK2 was identified, and LRRK2 is much more common in some

parts of our society, like the Ashkenazic population or the Basque population

in northern Spain and some parts of northern Africa.

But Parkinson's disease is an environmental disease.

It's what we're doing to ourselves. In some jurisdictions, Parkinson's disease

is recognized as an occupational disease.

In Germany, if you develop Parkinson's disease and you're a farmer,

that is a compensable condition from your occupation.

In Australia, we have big regional variants of Parkinson's disease.

Around Orange and the Central West, Parkinson's disease is incredibly common.

It's more common in the wine industry, where the use of fungicides is common.

You can go to Bunnings or any farm supply store and buy tomato dust.

In tomato dust, there's an agent called rotanone.

Rotanone is a mitochondrial poison that is strongly associated with Parkinson's disease.

There are very well-known neurologists, Bas Blom, in the Netherlands,

who advocates that his patients with Parkinson's disease get rid of all solvents,

industrial chemicals, pesticides, insecticides, herbicides, fungicides, out of the home.

In 1990, the Netherlands banned

a lot of chemicals that we still use in agriculture here in Australia.

The Netherlands is the only European country where the incidence of Parkinson's disease is decreasing.

Why is that important? Well, cause informs mechanism. Mechanism informs therapy.

And unfortunately, unlike the amyloid-based therapies that James and Alice have

in the clinic, we don't have anything yet that slows Parkinson's disease.

We were the only site of the Parkinson's Progression Marker Initiative from

the Michael Jay Fox, which is a big 20, 30-year study looking at the factors

that determine the progression of Parkinson's disease. It's still not sorted out.

What do we do in the clinic? How do we assess patients? I look after Maddie and I.

Poor old Maddie has had the misfortune of working with me for 27 years.

She needs a medal. Thank you.

I couldn't look after 800 people with Parkinson's disease without Maddie's expertise.

Similarly, I have a tremendous CNC, Jing Li, who helps me with our 250 patients

with motor neurone disease.

So the nursing input isn't valued.

It's not remunerated, but it's invaluable to me and to our patients.

So all of the stuff that Maddie was talking about, the aged care and the NDIS

stuff, she does all of that.

And we absorb that cost in neurology, but she spends hours and hours and hours

on this pitched battle with these government agencies.

She sort of played it down a little bit, but it is battle.

So what do we do in clinic?

Well, I look after 800 people with Parkinson's disease. They still come to me

from all around the place.

And it's quite amazing that some patients who've been on therapy for Parkinson's

disease for four, five, six, seven years have never had an MRI scan.

I have a unique gift for profanity, but I'm not going to swear.

But it is quite amazing that if you've got a disease like Parkinson's disease

and the initial neurologist doesn't do a scan, because sometimes neurologists think,

well, why do I need to do a scan? This is Parkinson's disease.

I don't need to do a scan. Well, you do need to do a scan because there are

lookalike conditions like normal pressure hydrocephalus, PSP,

multiple system atrophy, all these sorts of things.

So take a history, careful history, comorbidities, examine thoroughly.

There's a very gross staging system of Parkinson's disease,

called the Honan-Yah staging, and that's very gross.

So stage one is one side, stage two is two sides, stage three is that you're

starting to get impairment of balance, stage four is that you can't stand up,

and stage five is that you can't sit up.

So it's pretty gross.

We assess patients, there's a concept in Parkinson's disease called the magic 30 seconds.

So I walk out to the waiting room, I greet the patient in the waiting room,

because Because I'm a nasty person, my clinic room is the furthest from the waiting room.

So I get my 10,000 steps in every day.

Greeting the patient, greeting their partner, greeting their family,

watching them stand up, shaking their hand, putting them on the scale,

walking down the corridor, engaging in banter.

Watching them turn, watching them sit down. That's all assessment. And it's magic.

We check blood pressure. We weigh patients every time they come in because in

Parkinson's disease, you lose weight. You're in negative nitrogen balance.

It's very uncommon to see a fat person with Parkinson's disease. It does happen.

And some of the therapies tickle up your carbohydrate center.

But we weigh our patients every time they come in. We take their blood pressure.

We go through their medications very carefully.

Because sometimes in medicine, things become siloed and patients will go to

the cardiologist who puts them on beta blockers, which are not so great in Parkinson's

disease because they exacerbate orthostatic hypertension,

hypotension.

So we go through all their medicines.

We ask them about their vitamins, their supplements, their wool of bat and eye of newt.

Pyridoxine toxicity is something that we often see in clinic Where people are

taking way too much nature's own or blackmore's rubbish.

So spending time with patients, going through their medication,

what are they taking, what times are they taking their medicines,

how much are they taking, having sure that the patient is there with their partner to corroborate.

And that's also important with some of the therapies. So some of the therapies,

particularly the dopamine agonists, can tickle up behavioral changes.

So because these drugs talk to other parts of your brain, they can amplify behaviours

that may be hidden, like gambling, internet gambling.

It's a complete nightmare. Pokies, complete nightmare.

Hypersexuality, porn, internet. So you've got to interrogate your patients and

do it in a respectful way,

but with your antenna out, because when these things come out,

they can destroy families.

So being careful about the medicines and the doses that you use and talking about adverse effects.

Therapy. The cornerstone of therapy is levodopa.

I use levodopa as the first agent.

That's not necessarily the practice around Sydney or Australia.

Often they'll start with other therapies like monoamine oxidase,

B inhibitors or dopamine agonists.

I use levodopa because when people are symptomatic, we need to use the cheapest,

best, most effective therapy to reduce symptoms to the lowest level possible.

That's what you're trying to do.

There is longitudinal data that suggests that the better you treat patients,

you may help to slow the progression of Parkinson's disease.

That's a little bit controversial.

But you need to think about weight and gender. So if you have a 45-kilo,

70-year-old woman with Parkinson's disease, you're not going to use the same

starting dose as you're going to use in a 130-kilo,

50-year-old man.

So I had a 135-kilo fellow come to me a couple of years ago who his first neurologist

had him on Matapar 62.5, one, three times a day.

Homeopathic, did nothing. And he said, the medicine's not working.

And I said, well, it's not going to work.

It's weight-based. So you've got to give an appropriate dose for the person and their gender.

I tend to use principally only Levodopa, either Cinemet or Matapar.

And my preference is to use controlled release Cinemet.

Again, theoretically, the more

fluctuating you are with your levodopa in your blood and in your brain,

the worse you prime dyskinesia, where you see patients wriggling.

And curiously, we still don't understand why most dyskinesia in women starts

in their legs. You'll see them sitting there, one foot will be going.

And in men, it's mostly cranioservical. We don't understand that gender difference yet.

I often use very low-dose dopamine agonists, often in the form of Cifrol or Nupro, the patch.

And then look to adjunct therapies like monoamine oxidase B inhibitors like

Zadago, Cifinamide, or Risagiline, Azalect.

And then we have a couple of choices with catechol-O-methyltransferase inhibitors

with Comtan and Apicapone.

So I look at those as adjuncts they help your body to retain dopamine we also

need to think about other things that we might need to treat so depression anxiety is a common thing,

in Parkinson's disease so if we need to jump in and treat that,

But my preference, again, often is to use SSRIs rather than SNRIs,

because, again, without,

objective data to back it up, the SNRIs often turn up anxiety,

whereas SSRIs don't.

Constipation is universal. It is a movement disorder, pardon the pun.

But we approach that very simply.

Two minutes, I've got two minutes, goodness.

Fluid, you've got to have enough fluid. So I ask patients, what does your poo look like?

Is it rabbit pellets? Is it Maltesers?

If it's rabbit pellets or Maltesers, you don't have enough water because your

bowel slows down and it sucks fluid out of your poo.

So we use movacol, we use some form of senna like Nulax.

I happen to like Nulax, but it doesn't really matter.

And so it's very simple, enough water, movacol, constipation.

And again, you have to ask because patients won't necessarily volunteer it.

Okay management is not just

about pharmacotherapy so very early on we talk about only dead fish float with

the stream so getting patients to stay engaged involved active whatever that

is you got to ask people to do exercise according to what their preference is,

So sending my 135-kilo truck driver to Tai Chi and,

or Pilates, that's just not going to work. So you send him to,

you know, knock out Parkinson's disease, the punching guys.

So you've got to tailor exercise and you try and get patients to do at least

30 minutes of good going exercise a day.

There are some clinics and Maddie mentioned them.

So there's the various clinics that espouse a very active approach to Parkinson's disease.

And they're all really good. They're not for everyone. You've got to tailor it to the person.

It's got to be patient-centric in the context of their family,

so listen to what your patients are telling you.

Make sure that I try to get patients to come with their partner because that's

when you can really interrogate what's going on because someone's sitting next to them going, oh, yes.

So listening to what's going on in the clinic.

I have a few disclosures. NHMRC, MRFF, Shake It Up, and Michael J. Fox Foundation.

I sit on the scientific advisory board for Selozia, which is a startup here at Macquarie.

I have done some contract work for Biogen around therapy in motor neurone disease,

and I'm a full-time employee of Macquarie University.

Parkinson's is very common. It's more men than women, no two identical.

And we'll circulate the slides. You don't have to photograph them.

I'm happy for these to come to you all.

We need to consider advanced therapies. I haven't even touched on advanced therapies,

because that's a day in and of itself and maybe we can do that at some stage

because hopefully next year we'll be starting up DBS here at Deep Brain Stimulation

Surgery here at Macquarie and we already do some of the advanced therapies that

you might have seen on Channel 9 the Fos levodopa.

But why give something by a pump when a tablet works just as well?

I'd like to thank you all for coming on a Saturday morning, giving up your time,

because it really is fantastic to see faces of people that I have a correspondence

with about patients that I've looked after. So thanks for coming.