Exploring Parkinson's: From Gut Origin Theory to Advanced Treatment Options with Neurologist Dr Michele De Sciscio

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Did you realise that Parkinson's disease affects 200, 000 Australians, with 38 Australians being diagnosed with it every day?

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The incidence has increased over the last six years by 17 percent and 10 million people worldwide are suffering with it.

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It's a really important condition, which we all should know about, and may affect us in one way or another through family, friends or patients we may treat.

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Today we're going to hear about Parkinson's disease from Dr.

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Michele De Sciscio, a neurologist specialising in movement disorders at the Royal Adelaide Hospital.

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Welcome to Aussie Med Ed.

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G'day and welcome to Aussie Med Ed, the Australian medical education podcast, designed with a pragmatic approach to medical conditions by interviewing specialists in the medical field.

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I'm Gavin Nimon, an orthopaedic surgeon based in Adelaide, and I'm broadcasting from Kaurna Land.

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I'd like to remind you that this podcast is available on all podcast players, and is also available as a video version on YouTube.

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I'd like to start the podcast by acknowledging the traditional owners of the land on which this podcast is produced, the Kaurna people, and pay my respects to the Elders both past, present and emerging.

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I'd like to remind you that all the information presented today is just one opinion and that there are numerous ways of treating all medical conditions.

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Therefore, you should always seek advice from your health professionals in the area in which you live.

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Also, if you have any concerns about the information raised today, Please speak to your GP or seek assistance from health organisations such as Lifeline in Australia.

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Well it's my pleasure now to introduce Dr.

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Michele De Sciscio, a neurologist working at the Royal Adelaide Hospital.

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He graduated from the Flinders University in 2012 and then did basic physician training followed by advanced training in neurology.

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He's quite passionate about his research which he does in the both public and private sector and works for MedPlus where he's been working for the last 12 months.

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He's got two young children, as well as playing soccer for the Adelaide University Soccer Club in his 13th season.

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But he's going to talk to us about Parkinson's disease.

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Thanks Michele for coming on board.

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Now, we're all aware that Parkinson's disease leads to a tremor, can lead to an altered gait pattern, can lead to cognitive disturbances, often affects the older person, although I believe 20 percent of people newly diagnosed with Parkinson's are under the age of 50 years of age at diagnosis.

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Perhaps you can tell us a little bit more about Parkinson's disease.

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Hi Gavin, thanks for having me.

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It's a bit of a passion of mine, I sub specialised in it, so.

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As I've gone through the years and in learning about Parkinson's, what we're seeing is we're seeing a lot more people with Parkinson's and um, as our population gets older, we're kind of the prevalence of it is, is increasing.

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And for that reason, it's a significant disease and really important.

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I think statistically they're saying like one in 12 people , may have Parkinson's disease in the decades moving forward.

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So it's going to be quite a common thing for people to see, particularly, GPs.

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The pathophysiology of it has come a long way in recent years and it was this really interesting idea put forward maybe even 10, 15 years ago that the pathology starts in the gut.

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And as the years have gone on, we've got a lot more evidence of this.

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And the thought is that there's this gut brain axis.

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And basically the key.

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Pathology is a deposition of alpha synuclein in the substantia nigra, so deep part of the brain.

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And there's evidence to support the formation of alpha synuclein in the enteric kind of cells in the gut.

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So what happens is that, there seems to be this stimulus and whether that's environmental or just this change in the gut microbiome in people with Parkinson's disease and they develop.

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Alpha synuclein that kind of goes up the vagus nerve and deposits in the brain.

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And the evidence to support that is that they've found firstly, there's the prodromal symptoms of people with Parkinson's.

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For decades before they develop motor symptoms, we'll develop constipation and hyposmia or anosmia.

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So it lost a sense of smell.

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And then what they've found is that models in animals where they've induced Parkinson's, there's been alpha synuclein proteins in the gut early on and, and that kind of idea has progressed over time.

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And we've got a lot more evidence for that now.

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Right.

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Does it relate at all to what you actually eat, or is it actually purely a viral infection that occurs in the gut, or is it Not known yet.

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Yeah.

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So that has not known.

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There's been a few studies over the last two to three years looking at the gut microbiome of people with Parkinson's that's markedly different.

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There's a higher number of species that are related to pro inflammation and less of the species that are related to anti inflammation.

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They think that there's this issue with the gut permeability.

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So something happens, there's more permeability of, of, of toxins that come in or bacteria and that kind of stimulates.

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This abnormal production of alpha synuclein,, that's something that I didn't mention is that alpha synuclein is normal.

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It's cleared in the body, but there's this abnormal deposition.

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It accumulates in the brain deep in the substantia nigra and it can form Lewy bodies.

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And that leads to astrocytosis, so cell death and then dopamine destruction in a sense of the dopamine nerves get broken down and then you become dopamine deficient.

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Lewy body deposition or Lewy body dementia and Parkinson's are one of the same then?

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I, I assume there are two different conditions.

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Yeah.

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So I am still not a hundred percent clear, but my understanding is that alpha synuclein can deposit into clumps and then those clumps form Lewy bodies.

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So in Parkinson's disease, there's essentially these Lewy bodies that are formed in the deep part of the brain.

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And then as people advance with Parkinson's disease.

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They deposit more Lewy bodies around the rest of the brain, particularly in the, in the cortex.

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And that's when you develop Parkinson's disease, dementia, and that's what leads to the cognitive dysfunction, the increased daytime somnolence.

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And then you've got a different entity called Lewy body dementia or Lewy body disease is where this kind of this profuse deposition of Lewy bodies very early on.

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throughout the brain.

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It is technically an alpha synucleinopathy as well.

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So it's derived from alpha synuclein abnormality, which is the same as Parkinson's disease.

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I just see it as it's connected, but a very different entity in this, the presentation and the rapid progression of disease.

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So it's possible that the Lewy body dementia that occurs could be related to deposition generically around the brain, while Parkinson's is purely in the substantial nigra leading to dopamine deficiency.

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Yeah.

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Yeah.

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secondary to cell death.

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Correct.

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It starts like that.

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And then the idea is that in Parkinson's, as you progress and develop kind of dementia symptoms, there's deposition of Lewy bodies throughout the rest of the brain, but the way that they respond to treatment and the way that they present is very different.

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And there's other factors too that occur that, that predispose to Parkinson's.

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I believe things like genetics also can have a factor and also as exposure to pesticides, et cetera, do they all interrelate as well, or we're still coming to terms of how they all occur.

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Yeah, it's a very, very valid point that there is a genetic component of Parkinson's disease.

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So there are autosomal dominant, autosomal recessive inherited Parkinson's disease.

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It's a very small portion of what make up Parkinson's disease.

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The greater by far is a spontaneous or idiopathic Parkinson's disease where there's no kind of genetic predisposition.

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And you're right, there are some other conditions.

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That, I guess, can,, predispose to Parkinson's disease, in a sense.

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You mentioned pesticides.

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there is epidemiological, evidence to support there is some sort of connection between pesticides use and, increased risk of Parkinson's disease.

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The specific pesticide, hasn't really been determined, but I think from what I've read, it's just general pesticide exposure, increases the risk.

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So this all came from kind of studies in, farmers and they use pesticides quite a bit So when we talk about Parkinson's disease, we're talking about the neuro underlying etiology that people can have Parkinsonism or mimic Parkinson's disease if they're on antipsychotics.

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You can have disease within the basal ganglia that can look like Parkinson's disease, such as like a vascular cause like a stroke, or there are some kind of really rare metabolic conditions where there's breakdown of that basal ganglia and you look like you've got Parkinson's.

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So there are some very more rarer causes and that's really important to know when you're seeing someone with Parkinson's.

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, what about the use of illicit drugs?

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Does that have any association with Parkinson's disease?

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yeah, so there are several kind of,, animal studies looking at the role of methamphetamine and seeing that there is quite a lot of degeneration of the basal ganglia in mice exposed to methamphetamines.

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And , there are imaging studies, I think, that show that humans using methamphetamines, there is kind of degeneration of the dopaminergic neurons, throughout the brain.

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So there is an increased risk with methamphetamines there is also, a chemical called MPTP, which is essentially used to induce Parkinson's in, mice.

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And this chemical can be found in certain, illicit drugs.

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It tends to be a chemical that can be cut in, with the drug.

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, so that can be quite toxic.

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So that can actually cause degeneration of the nerve cells themselves rather than the actual other mechanism where you get, Lewy body deposition.

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Yeah, I presume it's primary,, degeneration of the, the dopaminergic neurons in the substantia nigra.

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It's used throughout Clinical trials to induce Parkinson's disease in mice.

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So yeah, it's extremely toxic.

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Well, that's a bit of a worry, isn't it?

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With the increased number of people using ice or methamphetamines and other drugs, there may be a factor for the future that will certainly create work for you.

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.

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No, that is true.

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There is concern that this methamphetamine epidemic is going to lead to a lot of health problems, one of them being increased incidence of Parkinson's disease down the track.

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How do you think about the symptoms and for the medical student, what would you be expected to describe as the classic symptoms for Parkinson's disease?

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Yeah, so it's a good point.

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There are a few different phenotypical presentations of Parkinson's disease.

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I think the one that we all are aware of is that hand tremor.

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Or a unilateral tremor.

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And that's really important.

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So Parkinson's disease will generally present with lateralizing symptoms.

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So typically there'll be one sided, so like a right hand tremor, or it might be one side quickly followed by the other with an asymmetry, yeah, the classic kind of rests, pill rolling tremor is when I think about Parkinson's disease.

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The other phenotype is this achinetic rigid.

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Uh, phenotype where people will present with one arm that's stiff or, or loss of dexterity of the hand.

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And then they, uh, feel they're quite stiff and rigid or, and then their movements are a bit.

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They're off, they're, they're shuffling, they're slow, um, or you can get another phenotype which is gait impairment with postural instabilities that there's a change in their gait and they might be shuffling, they might be slow and then there's the, they're, they're very unstable on their feet.

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They're the three kind of phenotypes that I think about Parkinson's disease.

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And then the history is really important.

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So talking about, I raised this earlier, that prodrome of constipation and hyposmia is really important.

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And there's another condition called REM sleep behavior disorder, which is very common in people with Parkinson's disease.

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And it's related to the degeneration of the deep part of the brain or within the midbrain.

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So they have this, it's basically dream reenactment behavior.

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So getting a history from the patient's, uh, partner.

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Where they're thrashing around or punching or kicking tends to precede any motor symptoms by decades.

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So that they've done studies where that combination of hyposmia and a REM sleep behavior disorder is highly prevalent in people with Parkinson's disease.

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So much so that if neither of those are present, you think, well, is this really Parkinson's disease?

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And, and this might be one of the Parkinson's and mimics or one of the atypical Parkinsonian syndrome.

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Is there any difference in the presentation of the younger person?

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I believe 20 percent of people who've get Parkinson's are under the age of 50 and of course the poster boy for Parkinson's.

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Michael J.

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Fox, very young age when he developed.

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Is that different to the standard person who's over the age of 50?

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Yeah, it's a very good point.

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Um, Gavin, so often the younger onset will present, uh, with dystonia.

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So, uh, you'll get a typical presentation of say someone saying that their, their walk is a bit funny.

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And not all the time, it tends to be quite intermittent.

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And what you'll do is you'll see when they're walking, you'll see this subtle kind of inversion of their ankle.

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Or you'll get someone who's saying that they're, they're having this dystonic posturing of their hand.

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And then I find in younger people, you tend to get more of the kind of akinetic type presentations, where they'll just say that their hands just stopped functioning properly.

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And one thing that often comes out of the history as well, and I didn't mention this, is with handwriting.

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Really important to ask about handwriting.

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Get a history of micrographia, that inability to maintain a particular size in the handwriting tends to diminish.

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So yeah, you're, you're spot on, the younger patients tend to present it slightly differently and it also is, is different in the way that you manage them, which I'm sure we'll talk about.

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And the gut symptoms you're talking about with constipation, are there any other type gut symptoms as well?

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Obviously, irritable bowel syndrome is quite a common scenario.

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Is that associated with it or is that just purely constipation they get?

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Yeah, I've, I've found that, and the teaching that I've always been taught is that it tends to be constipation.

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I don't really see that kind of like the irritable bowel or diarrhea as a main presentation.

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You can get, as with Parkinson's, a bit of gastroparesis, particularly as they advance on.

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That's, can be another symptom, so early feeling of satiety or,, stomach discomfort.

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And, for some people, the bowel symptoms can be their overwhelming symptoms to the point where they forget more so about their motor symptoms and they're very focused on their bowel symptoms.

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What's the natural progression for it?

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Obviously, you've mentioned at the end stages of it, there can be some dementia associated with it, but how does it tend to progress and how quickly does it progress in the average person?

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Obviously, people will vary depending on that.

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Yeah.

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It's a very good point.

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And then this is a question I get asked every time I diagnose someone with Parkinson's, I want to know what's their prognosis over the next five to 10 years.

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And I guess just from my experience, it varies, and I know that's a very kind of stock standard answer, but there are some genetic types, particularly there's an autosomal dominant type that presents with a GBA mutation, a Glucose Acidosis Mutation, and they present with a lot of cognitive issues and they tend to develop quite quickly or quite rapidly.

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But then the majority of people with Parkinson's, if they develop in their 60s, 70s, will often for the first five years, be well controlled with medications.

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And then the next five years, you might be tinkering with their medications and they will start to develop motor complications, sort of wearing off and dyskinesia.

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And then the statistics, I think around about 80 percent of people will develop dementia in between 10 to 20 years.

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with Parkinson's disease.

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But then you get some people when they get it at an older age, might progress a bit quicker.

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And then people that get it maybe in their younger years will be a little bit slower in their progression.

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So it's highly variable.

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And what about the diagnosis?

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Is it purely based on a clinical diagnosis?

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Is there any other special markers you can use or tests you can do to help diagnose it?

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Yeah, it's technically a clinical diagnosis.

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So in order to have Parkinson's disease, you have to have bradykinesia.

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So you need to have a decrementing, um, amplitude.

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Or speed of rapid movement.

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And the typical one that everyone would know about is the kind of rapid finger tap.

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So what we do is when we suspect someone had Parkinson's disease, we'll do a thorough history.

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And the importance of the history is to identify, for me anyway, I really focus on kind of the pro those prodromal symptoms.

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So if patients have got that hyposmia or REM sleep behavior disorder, I think about an alpha synucleinopathy.

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One of those is Parkinson's disease, then there's Lewy body dementia, and then there's multisystem atrophy, one of the offshoots of Parkinson's disease.

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If they're not present, you might think about what we call, uh, a tauopathy.

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That can be progressive supranuclear palsy or corticobasal degeneration.

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So the history is really important.

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And the other thing is, are there any red flags that this might not be Parkinson's disease, but one of the atypical Parkinsonian syndromes, such as MSA atrophy, progressive supranuclear palsy.

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And that would be things like.

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Early falls.

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So you wouldn't expect someone with Parkinson's disease to be falling within three to five years.

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You expect that to be a bit more later on down the track.

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Swallowing issues.

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If that's happening within the first three years, you'd be concerned that this may not be your stock standard Parkinson's disease.

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And early cognitive impairment as well, not typical with Parkinson's disease.

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You might get some mild cognitive issues, but profound cognitive problems you would worry about.

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So the history is really important there.

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But then it's the clinical examination, which is key.

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Looking for any features of bradykinesia, looking for any dystonia, so just observing the patient.

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Looking for any hypomimia or reduced facial expression.

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Looking for mouth being open, blink rate.

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These are all things that give you clues as could this be Parkinson's disease.

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But to clinically diagnose, you have to have that bradykinesia.

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I'm just going to go back a few steps to help my orthopaedic brain here to find some of these terms just to make it a little bit easier for me.

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No, no, no.

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Of course.

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I think I'm probably getting a bit too excited and ahead of myself.

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So you've got, the way that I break things up, you've got a hypokinetic disorder or you've got a hyperkinetic disorder.

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Hypokinetic, we think a lot about kind of slowness of movement, bradykinesia, where as you rapidly do things, it slows down, then you've got hyperkinetic movement.

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And one of them would be dystonia.

00:18:05.839 --> 00:18:14.089
In that normally when say your muscles are meant to be at rest, they're hyperkinetic and you get some kind of overactivity of a muscle and it starts turning.

00:18:14.630 --> 00:18:19.029
And that, that there can be a prominent feature in someone with.

00:18:19.829 --> 00:18:25.170
Early onset Parkinson's disease, or it can develop in as the disease progresses.

00:18:25.740 --> 00:18:30.690
Uh, and then another hyperkinetic movement issue would be, uh, dyskinesia.

00:18:31.339 --> 00:18:34.720
So dyskinesia is a condition that people with Parkinson's disease.

00:18:35.025 --> 00:18:47.315
Developed particularly after about five years of treatment where they get this kind of riding movement and, and you would see people that are well medicated with Parkinson's disease, but they're riding around quite a bit.

00:18:47.434 --> 00:18:55.035
And the idea behind that is that it's this dysregulation of dopamine receptors in the brain through being pulsed with levodopa.

00:18:55.375 --> 00:18:58.075
So eventually they become dysfunctional.

00:18:58.420 --> 00:19:03.630
And then when they're given levodopa and they're activated, they produce too much movement and they become dyskinetic.

00:19:05.410 --> 00:19:07.420
You also mentioned a differential.

00:19:08.299 --> 00:19:08.680
Yeah.

00:19:08.680 --> 00:19:14.480
So with Parkinson's disease, you've got these, um, offshoots or the atypical Parkinsonian syndromes.

00:19:14.480 --> 00:19:17.880
And one of them is the progressive supranuclear palsy.

00:19:17.880 --> 00:19:19.420
One of them is multi system atrophy.

00:19:19.420 --> 00:19:21.309
One of them is corticobasal degeneration.

00:19:21.890 --> 00:19:31.799
So, they're the much rarer forms of Parkinsonism, so that being the umbrella term, and Parkinson's disease being one condition in these three.

00:19:32.119 --> 00:19:34.450
Are there atypical Parkinsonian syndromes?

00:19:34.779 --> 00:19:43.400
So yeah, they tend to present in the kind of the fifties, sixties, those decades, they're much more kind of rapid in their progression.

00:19:43.809 --> 00:19:47.950
So I think the mean life expectancy is about nine years.

00:19:48.250 --> 00:19:49.650
So really quite nasty.

00:19:49.859 --> 00:19:55.559
They don't respond well to levodopa, which is the key treatment in Parkinsonism.

00:19:55.869 --> 00:20:16.680
And the way that I've always been taught and I think about it is that if Parkinson's disease is like a pre synaptic dopamine problem where you can't release dopamine, and then you've got these atypical Parkinsonian syndromes where it's a post synaptic problem where you can have as much dopamine as you like, but those post synaptic nerves are damaged.

00:20:16.690 --> 00:20:18.589
So they're not responding to the dopamine.

00:20:19.414 --> 00:20:24.144
And that's why people with PSP, the overwhelming majority won't respond to Lever Dover.

00:20:24.144 --> 00:20:26.325
I think it's something like 20%.

00:20:26.785 --> 00:20:32.055
MSA is a little bit different in that they tend to respond, a majority of people tend to respond quite well.

00:20:32.085 --> 00:20:38.164
So I think it's something like 50%, not to the degree that you get in Parkinson's disease, but there is some response.

00:20:38.555 --> 00:20:50.515
And then corticobasal degeneration, which is quite rare, which hardly ever see, that typical presentation is with this kind of adding limb where one arm is riding around the person, like the person's not in control of that hand.

00:20:50.734 --> 00:20:53.724
They generally don't respond very well to levodopa either.

00:20:54.674 --> 00:21:02.894
Now, obviously you've touched upon the treatment option of levodopa, are there any other new forms of treatment for Parkinson's now, or is that still the mainstay?

00:21:03.214 --> 00:21:04.694
Yeah, that's still the mainstay.

00:21:04.755 --> 00:21:10.015
In anyone who suspects it's got Parkinson's disease, I'll generally start with levodopa.

00:21:10.315 --> 00:21:15.855
There is a thinking that in young onset, so people less than 50.

00:21:17.085 --> 00:21:27.505
Uh, you can start with, a dopamine agonist., and the idea behind that is to try and limit the amount of levodopa that, a patient is being exposed to.

00:21:27.884 --> 00:21:36.134
In young onset Parkinson's disease, there's always that risk of developing a dyskinesia when you exceed a higher level of levodopa.

00:21:36.134 --> 00:21:43.815
So some clinicians will start a dopamine agonist and if they get good control of symptoms you introduce some levodopa down the track.

00:21:44.734 --> 00:21:51.224
Pretty much in every patient I'll start with levodopa because it also provides useful information that if they improve or they respond.

00:21:51.839 --> 00:22:01.480
It gives further evidence that we're dealing with Parkinson's disease, because as I mentioned, the atypical Parkinsonian syndromes are less likely to respond to levodopa.

00:22:02.079 --> 00:22:06.589
It's just about that level of what, what's that, what's a safe levodopa level.

00:22:06.589 --> 00:22:15.390
And I know the teaching that I've always been taught is that you would have exceed over 400 in someone who's young,, because of the risk of developing dyskinesia down the track.

00:22:15.460 --> 00:22:20.519
Risk factors of developing dyskinesia down the track are if you're female, if you're young, and if you're thin.

00:22:21.095 --> 00:22:28.825
So,, the thin, young female, I would very be reluctant to kind of exceed, , 300 of levodopa.

00:22:29.005 --> 00:22:34.424
And that's really important because as a general practitioner, if you're seeing someone who you think has got Parkinson's disease.

00:22:35.019 --> 00:22:37.599
And, you need to refer them to a neurologist.

00:22:37.599 --> 00:22:38.890
They may not be seen for six months.

00:22:38.910 --> 00:22:44.509
It'd be reasonably safe to start them on a low dose of levodopa, generally half a tablet three times a day.

00:22:44.980 --> 00:22:48.720
And you would increase that maybe in two weeks to one tablet three times a day.

00:22:48.720 --> 00:22:52.460
You could even, if there's no response after that, go to one and a half tablets three times a day.

00:22:52.865 --> 00:22:56.964
And know that you're within that safe reign, even if it's someone young.

00:22:57.775 --> 00:23:00.785
So that's a little bit of advice I'd give in terms of treatment.

00:23:01.505 --> 00:23:04.275
Are there any other treatment options apart from levodopa though?

00:23:04.375 --> 00:23:05.105
Yeah, of course.

00:23:05.164 --> 00:23:08.835
So they're kind of the main treatments that I use.

00:23:08.835 --> 00:23:09.884
You've got your levodopa.

00:23:10.134 --> 00:23:11.535
You've got your dopamine agonist.

00:23:11.545 --> 00:23:13.244
So that's Pramipexole.

00:23:14.059 --> 00:23:15.269
Or reticotine.

00:23:15.529 --> 00:23:18.160
And they work quite well with the levodopa.

00:23:18.400 --> 00:23:23.640
They're both dopamine agonists activating the dopamine receptors and dopamine is also doing that.

00:23:23.640 --> 00:23:24.640
So they're working together.

00:23:25.039 --> 00:23:27.720
You've also got a monoamine oxidase inhibitor.

00:23:27.779 --> 00:23:31.509
The ones that we use a lot are Rasagiline and there's a new drug called Cefenomide out.

00:23:31.910 --> 00:23:37.609
They inhibit the breakdown of dopamine in the brain to theoretically enhance the level there.

00:23:37.994 --> 00:23:50.085
And then you've got some of, you've got drugs like Entecapone or Picapone, that COMT inhibitors, which also again try and inhibit the breakdown of dopamine to enhance the longevity of levodopa.

00:23:50.365 --> 00:23:54.724
They're the fundamental treatment options for people with Parkinson's disease.

00:23:54.944 --> 00:23:58.244
And then you've got several kind of advanced therapies.

00:23:58.555 --> 00:24:06.234
that you can look at with people for Parkinson's that have had it for several years that may be developing some motor complications.

00:24:06.234 --> 00:24:10.575
And when I say motor complications, I'm talking about when their medication is switching off.

00:24:10.704 --> 00:24:14.565
So what we call off time or if they're developing dyskinesia.

00:24:16.214 --> 00:24:23.625
And where do the physical agents come into it, like the nerve stimulators, are they proven or are they still on the experimental side of things?

00:24:23.825 --> 00:24:25.255
Yeah, good question.

00:24:25.275 --> 00:24:28.644
The proven treatments that we use are deep brain stimulation.

00:24:28.984 --> 00:24:34.994
So that's been around for decades and has proven to be a very useful advanced therapy.

00:24:35.394 --> 00:24:37.684
It is indicated in people.

00:24:38.045 --> 00:24:46.325
that have got a good dopamine responsiveness, but who are developing, as I mentioned, those kind of motor complications of being on medications longer term.

00:24:46.605 --> 00:24:47.384
So that's the first one.

00:24:47.384 --> 00:24:51.404
The second one is it might be people that have got tremor refractory Parkinson's disease.

00:24:51.694 --> 00:24:56.025
So there are unfortunately some people that their tremor is just not responsive to medication.

00:24:56.025 --> 00:24:58.605
So they'll look at deep brain stimulation for these people.

00:24:59.184 --> 00:25:03.275
The other type of treatment is levodopa continuous intestinal gel.

00:25:03.724 --> 00:25:12.684
So a, a tube is essentially put into the stomach and that kind of infuses levodopa gel continuously over a, over a wake period.

00:25:13.119 --> 00:25:21.160
And the idea is that there is a more kind of level, steady release of dopamine into the body rather than peaks and troughs that you get with oral medication.

00:25:21.670 --> 00:25:26.220
And then you can get a subcutaneous infusion of a dopamine agonist.

00:25:26.740 --> 00:25:29.529
And that works very effectively as well.

00:25:29.539 --> 00:25:39.220
The contraindication for that may be someone who's developing, say, profound cognitive impairment or hallucinosis because a dopamine agonist can make that worse.

00:25:39.670 --> 00:25:46.569
But all, all three treatments have their benefits and their pros and cons and it kind of go through each individual patient.

00:25:46.859 --> 00:25:52.849
There are some new kind of advances looking at fecal microbiota transplantation for people with Parkinson's disease.

00:25:53.150 --> 00:26:03.500
And that goes back to that kind of theory that this all starts in the guts and the evidence that people with Parkinson's have an abnormal or a different gut microbiome.

00:26:04.039 --> 00:26:15.000
So, that's being explored, that's really exciting, um, and there's a lot of other kind of drugs on the horizon looking at disease modifying therapy rather than just symptomatic therapy.

00:26:15.799 --> 00:26:19.750
Yeah, are there any biological type agents that actually have any role in Parkinson's disease at all?

00:26:20.210 --> 00:26:24.069
Yeah, it's a good question, and, and look, I'm not familiar with the current evidence.

00:26:24.109 --> 00:26:31.140
I do know that there are some study, like phase one studies, looking at antibodies against kind of alpha synuclein.

00:26:31.529 --> 00:26:43.099
Um, I'm not sure if any kind of phase two studies have been done, um, but nothing that I'm aware of on the horizon, but it is an exciting kind of area and theoretically makes sense.

00:26:43.109 --> 00:26:51.140
So if you can block the abnormal production of alpha synuclein or if that you do have these aggregates in the brain, is there any way of cleansing that?

00:26:51.170 --> 00:26:55.700
It's a very exciting area and I'm sure that these areas are being looked at.

00:26:56.490 --> 00:26:56.950
Excellent.

00:26:57.819 --> 00:26:58.190
All right.

00:26:58.519 --> 00:27:02.420
What about the side effects of the medications we're actually using to treat Parkinson's disease?

00:27:02.519 --> 00:27:07.670
Can the treatment with Parkinson's cause any, either depression or hypomania episodes as well?

00:27:07.670 --> 00:27:09.220
Is there any association with that at all?

00:27:09.869 --> 00:27:10.769
Yeah, it's a good question.

00:27:10.839 --> 00:27:14.569
So in terms of levodopa, it's a fairly kind of benign drug.

00:27:14.579 --> 00:27:19.589
The theoretical side effects are that it can cause a postural blood pressure drop, but I rarely ever see that.

00:27:19.829 --> 00:27:22.549
You can get dopamine dysregulation syndrome.

00:27:22.869 --> 00:27:29.170
So in patients that are taking too much levodopa, and that tends to be around the 1000 milligrams per day.

00:27:29.170 --> 00:27:31.250
So obviously these are people that are quite advanced.

00:27:31.720 --> 00:27:34.710
You can get people getting this, I guess, addiction to taking dopamine.

00:27:35.210 --> 00:27:37.694
So they'll often Take high levels.

00:27:37.974 --> 00:27:42.005
And I think the idea is that there may be some kind of potential euphoric feeling.

00:27:42.005 --> 00:27:59.184
I'm not sure as some what happens, but they, they do tend to overdo their medications and it's something ways to be wary of, and there's this condition called punding where people with Parkinson's disease, when they get a high level of dopamine, usually around that 1000 milligrams, will develop these kinds of pointless.

00:27:59.265 --> 00:28:01.625
repetitive exercises.

00:28:01.944 --> 00:28:09.315
So it must be some dopaminergic pathway driving this kind of desire to, to do some sort of particular ritualistic action.

00:28:09.555 --> 00:28:14.464
So the dopamine agonist, you always have to be very careful about an impulse control disorder.

00:28:14.805 --> 00:28:25.984
So particularly the things that you need to be mindful of is it can cause sexual disinhibition, it can cause gambling, it can cause excessive eating, hoarding and shopping.

00:28:26.339 --> 00:28:40.000
And this can happen to any patient, the one that most risk a male, young, and if they had a tendency to do these behaviors before, but it's something as a clinician, um, I always need to be responsible about when I'm prescribing.

00:28:40.319 --> 00:28:44.859
And I always ask the GP's assistant to keep an eye out for these things.

00:28:44.859 --> 00:28:52.710
And you always rely on the partner to tell you if they've bought 10 yachts in the last year because some, some ludicrous things can happen.

00:28:53.150 --> 00:28:55.819
In terms of the monoamine oxidase inhibitors.

00:28:56.170 --> 00:29:02.829
Obviously, you need to be mindful of if someone's already on an antidepressant or a higher dose of antidepressant, there's always that risk of serotonin syndrome.

00:29:03.490 --> 00:29:16.200
I remember looking at some literature from Spain where they were looking at the addition of a monoaminoxidase inhibitor with an antidepressant in people with Parkinson's disease that generally didn't lead to serotonin toxicity.

00:29:16.430 --> 00:29:17.430
So that's fairly safe.

00:29:18.180 --> 00:29:26.130
And then there's always that mentioned about the, I guess the side effects or complications of high dose of levodopa being inducing dyskinesia.

00:29:26.690 --> 00:29:34.549
And, and sorry, it can also in, in particularly older patients, when you're starting someone on agonist, it can cause, nausea.

00:29:34.890 --> 00:29:41.950
And as mentioned that the postural blood pressure drops and also can cause some peripheral edema, particularly with the dopamine agonist.

00:29:43.059 --> 00:29:43.589
Excellent.

00:29:44.670 --> 00:29:47.650
What about the team that helps look after a person with Parkinson's?

00:29:47.710 --> 00:29:49.769
As a neurologist, who do you actually want to involve with?

00:29:49.779 --> 00:29:54.640
I presume you want to involve a nurse or a support agent in it, partner of the person.

00:29:54.759 --> 00:29:57.869
Who makes up a team to help support someone with a diagnosis?

00:29:58.255 --> 00:30:02.605
Yeah, we, in the public system, rely very heavily on the Parkinson's nurses.

00:30:02.924 --> 00:30:08.855
When I diagnose someone with Parkinson's disease, I always try and link them in very early with the Parkinson's nurses.

00:30:09.055 --> 00:30:18.375
And in the private sector, there's Parkinson's SA, which is a phenomenal organization who have recently employed, I think it's four full time nurses for the community.

00:30:18.704 --> 00:30:31.549
So linking them in very early is, is super important because Often I find patients, they leave the room with all this information and it's very overwhelming because they've just been told that they've got Parkinson's disease, a neurodegenerative disorder.

00:30:31.650 --> 00:30:38.599
So linking them in with nursing is really important, , there is really good evidence for physical activity in the treatment of Parkinson's disease.

00:30:38.609 --> 00:30:47.515
So I often, suggest linking them in early with, with a physiotherapist, usually a neurophysio who, who deals with Parkinson's disease and knows what to look for.

00:30:47.565 --> 00:30:54.184
And some, I've had some patients that have seen a physio and simply just changing what frame they use has dramatically improved their fall.

00:30:54.234 --> 00:30:55.144
That's really important.

00:30:55.164 --> 00:31:14.750
I also link people with speech pathologists sometimes when there's concerns about swallowing, that tends to be more advanced, but it's really important having this kind of team around There's kind of the movement aspect of things, which we as neurologists will deal with, then physios, but there's also a lot of psychological.

00:31:15.305 --> 00:31:17.894
Impact of being told you've got Parkinson's disease.

00:31:17.904 --> 00:31:20.815
Linking with a psychologist can be really important as well.

00:31:21.045 --> 00:31:23.515
There's a lot of co morbid anxiety, depression.

00:31:23.835 --> 00:31:30.974
So sometimes we seek the input of psychiatrists, particularly when there's some cognitive issues as well, leading to kind of behavioral problems.

00:31:31.434 --> 00:31:42.555
So there is this, this big team that's really needs to be involved to look after to patients and then also their loved ones, because there's a lot of care burden as well, being with someone who's got Parkinson's disease.

00:31:42.595 --> 00:31:44.595
This is an association with gut disturbance.

00:31:44.990 --> 00:31:47.039
Are there any foods that people should avoid?

00:31:47.059 --> 00:31:50.140
Are there any particular foods that are bad for Parkinson's?

00:31:50.960 --> 00:31:52.069
Yeah, it's a really good question.

00:31:52.079 --> 00:31:54.660
I'm not familiar with any kind of bad foods.

00:31:54.730 --> 00:32:01.420
I know that there's a study that's come out recently supporting the use of a particular probiotic to help with Parkinson's disease.

00:32:01.430 --> 00:32:04.974
So the gut function, high fiber is really important in people with.

00:32:05.355 --> 00:32:10.075
Parkinson's disease to help that kind of regularity of bowel movement.

00:32:10.434 --> 00:32:19.684
So having said that, dietician, having someone who can provide expertise on how to get the gut functioning better is a really important and useful tool as well.

00:32:19.714 --> 00:32:25.894
So I'm not familiar with foods that shouldn't be eaten, but I can think about more about what foods could help with bowel function.

00:32:26.835 --> 00:32:27.375
Excellent.

00:32:28.065 --> 00:32:29.994
Where's the research going for this?

00:32:30.025 --> 00:32:33.505
You've mentioned in passing about the use of fecal transplants.

00:32:33.545 --> 00:32:47.214
Yeah, that's a really interesting area and something that I know quite well because I've just finished running a pilot study in patients with Parkinson's disease and if there's any benefit of fecal microbiota transplantation, the theory behind it is quite robust.

00:32:48.079 --> 00:33:04.089
This is just an initial pilot study and we showed, uh, we've yet to publish a result, but what we think we're seeing is some sort of trend in, in, in a bit of improvement in some of the non motor aspects of Parkinson's disease, quality of life, mood, sleep, those type of things.

00:33:04.319 --> 00:33:10.424
And I know that there are some very small other pilot studies that have been done around the world looking at the benefits of Parkinson's.

00:33:10.744 --> 00:33:13.244
of FMT or fecal microbiota transplantation.

00:33:13.244 --> 00:33:17.424
I think that large, very large studies are needed for that.

00:33:17.654 --> 00:33:22.505
There are some other,, evidence to support subcutaneous use of levodopa.

00:33:23.464 --> 00:33:26.565
So I know that there's some very good evidence for that as well.

00:33:26.605 --> 00:33:33.434
And I think that potentially is on the horizon, but then, yeah, going back to looking at what are the disease modifying approaches and.

00:33:33.944 --> 00:33:43.845
Whether we can use a biologic for alpha synuclein, maybe a vaccine perhaps that targets the alpha synuclein kind of production.

00:33:44.154 --> 00:33:46.315
That is a potential, uh, method.

00:33:46.734 --> 00:33:50.615
So yeah, some potential avenues for advancement.

00:33:52.384 --> 00:33:52.785
Brilliant.

00:33:52.785 --> 00:33:56.105
So why do we think it's increasing in the incidence then?

00:33:56.759 --> 00:34:04.079
The food we're eating, yeah, it's a, it's a good question and something that,, one of my colleagues asked me about and, and I'm not sure of the answer.

00:34:04.130 --> 00:34:25.369
I do wonder, I'll put it down to just as a general population's getting older and it tends to be an old person's disease, but, but there has to be some sort of environmental factors, I think anyway, particularly now looking at the gut microbiome and the changes that are there is that, is this some sort of toxin driven thing or infective driven thing that kind of.

00:34:25.835 --> 00:34:31.184
triggers this process and therefore it's just becoming more and more prevalent.

00:34:32.175 --> 00:34:43.885
And as a neurologist treating movement disorders, I presume Parkinson's is the vast majority of your diagnoses that you make, but what are the other conditions that medical students should be aware of that can cause movement disorders as well?

00:34:44.445 --> 00:34:46.644
Yeah, the ones that I see a lot of are tremor.

00:34:47.135 --> 00:35:05.960
And like you said, that kind of Links with Parkinsonism, but I see a lot of essential tremor, and I could do a whole nother podcast on, on essential tremor and dystonic tremor, but they're, they're the main ones because people will often present with particularly younger people with a tremor,, and it'll be usually bilateral and that kind of gives you a bit of the clue.

00:35:06.389 --> 00:35:08.500
And the biggest concern is this Parkinson's disease.

00:35:08.860 --> 00:35:13.309
So, that's probably the second biggest group of people that I see.

00:35:13.550 --> 00:35:18.139
And then I'll see a lot of hyperkinetic movement disorders.

00:35:18.139 --> 00:35:26.590
So a cervical dystonia where I'll see people with their kind of head being turned to one side or a bit of a head bob.

00:35:26.909 --> 00:35:31.239
I might see hemifacial spasm or blepharospasm, blinking of the eyes.

00:35:31.489 --> 00:35:34.019
So I see a lot of those kind of disorders.

00:35:34.394 --> 00:35:40.144
As the other kind of group, but that kind of pales in comparison to the frequency of people that I see with Parkinson's disease.

00:35:40.144 --> 00:35:44.474
And that just could be because I'm a Parkinson's specialist and that's what I get referred a lot of.

00:35:45.514 --> 00:35:45.695
Yeah.

00:35:45.735 --> 00:35:48.994
The cervical dystonia, I've seen a couple of people come along with that as well.

00:35:48.994 --> 00:35:51.505
So it's not something that rare, I would have thought.

00:35:52.514 --> 00:35:55.695
Yeah, no, it's, you do see, you do see it occasionally.

00:35:56.135 --> 00:36:00.184
And it's an interesting one because it tends to be underdiagnosed or misdiagnosed.

00:36:00.184 --> 00:36:00.594
So it's.

00:36:00.974 --> 00:36:18.000
Patients, you often hear the journey of patients having neck pain, seeing physios, seeing orthopaedic surgeons and then someone's kind of clues in on your head's been turned now for a decade and you look at photos and they're in the photos, they've always got either torticollis or latricollis.

00:36:18.360 --> 00:36:22.300
And then someone will feel the musculature around the neck and, and it's, it's, it's rock hard.

00:36:22.769 --> 00:36:27.199
And then, you then get referred these patients and, and see them in a cervical dystonia.

00:36:27.199 --> 00:36:30.599
I think it's a really important condition for us all to know about.

00:36:31.170 --> 00:36:41.260
Even myself as an orthopaedic surgeon have seen a patient and diagnosed someone who presented previously to me and who obviously had Parkinson's disease, but which had been remained undiagnosed until I saw him.

00:36:41.679 --> 00:36:45.519
So some of those things that actually might present to anyone in any particular situation.

00:36:45.829 --> 00:36:47.139
So it's great hearing all about it.

00:36:47.684 --> 00:36:54.264
One patient comes to mind that they went to see their cardiologist for chest pain and the cardiologist was like, that's the second problem you have.

00:36:54.264 --> 00:36:59.885
The first problem is you're shaking and you're shuffling and it was for that reason that led to seeing me.

00:36:59.894 --> 00:37:06.554
So I think it's one of those things where Every clinician should be on the lookout for, and it is a clinical diagnosis.

00:37:06.635 --> 00:37:14.724
Being able to spot those clues is really important, whether or not you diagnose them or whether or not you just point them into the right direction, it's really important.

00:37:16.434 --> 00:37:19.545
Look, it's been fantastic having you on board today, so I really appreciate it.

00:37:20.190 --> 00:37:22.389
Thank you very much for your time and it's great to have you with us.

00:37:22.860 --> 00:37:23.949
Thanks Gavin, I really appreciate it.

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Thank you very much for listening to our podcast today.

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I'd like to remind you that the information provided is just general advice and may vary depending on the region in which you are practicing or being treated.

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If you have any concerns or questions about what we've discussed, you should seek advice from your general practitioner.

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I'd like to thank you very much for listening to our podcast and please subscribe to the podcast for the next episode.

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Until then, please stay safe.