Parkinson’s Disease
Parkinson’s Disease Prof Dominic Rowe
In this podcast, Professor Dominic Rowe provides an extensive overview of Parkinson's disease, emphasizing its historical development, clinical features, treatment options, and the importance of a patient-centered approach in managing the condition. The discussion begins with a historical context, tracing the early identification of Parkinson's disease back to 1817 when surgeon James Parkinson described a set of symptoms he termed "paralysis agitans." This foundational description laid the groundwork for future research, including the significant contributions of Jean Charcot and Arvid Carlson, the latter identifying dopamine deficits as a pivotal aspect of the disease. Rowe notes that although dopamine deficiency is key, Parkinson's disease encompasses much more than just this neurotransmitter’s loss.
The lecture progresses into an exploration of the myriad clinical features associated with Parkinson's disease. Rowe highlights that over 200 symptoms can manifest, underscoring the variability in how the disease presents among individuals. He points out that many patients may not exhibit the classic tremor, which can lead to delayed diagnoses. The importance of recognizing premotor symptoms such as REM sleep behavior disorder, olfactory deficits, and mood changes is emphasized, illustrating how these early signs can precede motor symptoms by many years and complicate timely intervention.
As Rowe discusses treatment strategies, he underscores levodopa as the cornerstone of therapy, along with additional adjunct medications that may help manage various symptoms. The need to tailor treatment based on the individual's characteristics, such as weight and gender, is articulated, reiterating that effective management must consider a patient's complete medical history and present condition. Rowe also addresses the necessity for routine assessments, advocating for thorough examinations that go beyond surface-level interactions to encompass holistic patient care.
The environmental factors contributing to Parkinson's disease are brought to the forefront, with Rowe elucidating the links between occupational exposure and instances of the disease. This discussion ties into broader epidemiological factors, illustrating that while Parkinson's disease has genetic underpinnings, it is largely influenced by environmental elements. Rowe highlights the stark increase in Parkinson's disease prevalence in Australia over the years, calling attention to the implications for healthcare systems and research.
In the latter part of the lecture, Professor Rowe stresses the importance of a patient-centric approach in treatment. He advocates for active engagement in exercise tailored to the individual’s abilities and preferences, promoting lifestyle adjustments that can enhance the quality of life for patients. The necessity of effectively managing non-motor symptoms such as depression and anxiety is discussed, along with pragmatic solutions like dietary modifications to address common issues like constipation.
Rowe concludes with a nod to future directions in Parkinson's disease therapy, mentioning advancements and the potential inclusion of deep brain stimulation as a treatment option at Macquarie University. Throughout the presentation, there is a palpable passion for the subject, as Rowe expresses gratitude for the audience's engagement and the opportunity to share knowledge about this increasingly prevalent neurological disorder.
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Transcript
So, it's my very great privilege and honour to introduce Professor Dominic Rowe.
Speaker:I don't think Dominic needs a lot of introduction to this audience,
Speaker:but Dominic is the inaugural Professor of Neurology here at Macquarie University,
Speaker:and he has both clinical and research expertise in the fields of motor neuron disease,
Speaker:Parkinson's disease, and other neurodegenerative diseases.
Speaker:Today, he's going to give us an update on Parkinson's disease,
Speaker:and I'll let you take it away, Dom. Thanks, James.
Speaker:I've got 20 minutes to do Parkinson's disease, so this is going to be really quick.
Speaker:What I thought I'd do first is to just put the Parkinson's disease in a historical context.
Speaker:So in 1817, a surgeon in East London, in the Sound of Bowbells,
Speaker:a true East Ender called James Parkinson,
Speaker:described six patients, two of whom were his patients and four of whom he saw in the street.
Speaker:And he described the constellation of symptoms that he codified as paralysis agitans.
Speaker:So he called it paralysis agitans.
Speaker:The father of modern neurology, Jean Charcot, read James Parkinson's tome,
Speaker:and he coined the term Parkinson's disease.
Speaker:It was until 100 years after Parkinson first described paralysis agitans that
Speaker:a PhD student in Paris actually identified the pathologic substrate of Parkinson's
Speaker:disease, a chap called Tritiakov,
Speaker:who systematically went through the brains of patients with Parkinson's disease
Speaker:and first identified that the substantia nigra was affected by Parkinson's.
Speaker:The English and the Americans didn't believe it. It was the Swedish who made
Speaker:the next huge leaps forward in Parkinson's disease.
Speaker:And that was Arvid Carlson in the 50s and 60s, who was able to demonstrate that
Speaker:it was a deficit in the major transmitter dopamine, as well as other transmitters.
Speaker:So we falsely think of Parkinson's disease as just a dopaminergic deficit, but that's not all.
Speaker:So Arvid Carlson actually after describing it in the 50s and 60s finally won
Speaker:the Nobel Prize anyone know the year that he won the Nobel Prize for identifying dopamine deficit,
Speaker:well you know good things come to all who wait the year 2000 was,
Speaker:He got the Nobel Prize for Physiology and Medicine for identifying.
Speaker:And Oli Hornikovic, who was a very famous Austrian pathologist and neurochemist
Speaker:who described it at exactly the same time, was incredibly pissed off because
Speaker:Carlson got the Nobel Prize and he didn't.
Speaker:In 1965, George Kotsius, who was a resident working in New York City,
Speaker:introduced levodopa as therapy.
Speaker:So if it's a dopaminergic deficit, give people dopamine, they'll get better.
Speaker:Well, dopamine doesn't cross the blood-brain barrier.
Speaker:But George Kotsius worked out that if you gave a precursor of dopamine,
Speaker:leave it OPA, that that crosses the blood-brain barrier. So it wasn't Oliver Sacks.
Speaker:Wasn't him. It was George Kotsius in 1965, so the year I was born.
Speaker:It's still the best therapy, levodopa.
Speaker:So Merck Sharpen Dome introduced carbidopa, so carbidopa produces a thousand-to-one
Speaker:gradient for levodopa to get into your brain.
Speaker:And Roche produced benserazide about three years later, which is why most levodopa
Speaker:therapy is in the form of levodopa, carbidopa,
Speaker:90% and 10% because MSD got there first.
Speaker:But however, Matapar has its place and I'll come to that.
Speaker:So what are the clinical features of Parkinson's disease?
Speaker:Well, there are more than 200 clinical features of Parkinson's disease and there
Speaker:are no two patients who are the same.
Speaker:There's a very long prodrome in Parkinson's disease.
Speaker:REM sleep behavior disorder that Alice touched on. Hyposmia Constipation.
Speaker:Vivid dreams, behavioral change, depression, anxiety, all in the premotor phase
Speaker:of Parkinson's disease.
Speaker:By the time you present with tremor, slowness or stiffness, you've lost 70%
Speaker:of your brain's dopamine.
Speaker:You've had the disease for 10 to 20 years.
Speaker:Parkinson's disease is a whole-body disease. Skin changes, hair changes,
Speaker:bone changes, vitamin D changes, hepatic changes, gut changes.
Speaker:30% of people with Parkinson's disease never have tremor, ever.
Speaker:So bradykinetic rigid Parkinson's disease often is diagnosed much later.
Speaker:And there are quite a few mimics for Parkinson's disease. And it's important
Speaker:to remember that other diseases like PSP, progressive supranuclear palsy,
Speaker:which is characterized by early significant falls.
Speaker:So if your patient looks Parkinsonian and they're falling in their first year,
Speaker:then it might not be Parkinson's disease.
Speaker:Multiple system atrophy has several different forms, but the most common of
Speaker:which looks like Parkinson's disease, but it's a much worse disease.
Speaker:Normal pressure hydrocephalus, and it's important to remember that some drugs,
Speaker:notably valproate, epilim.
Speaker:So perhaps once or twice a year, I have a patient who's sent to me with a diagnosis
Speaker:of Parkinson's disease, and they've been on epilim, and you stop their epilim,
Speaker:and their Parkinson's disease goes away.
Speaker:And then there are other mimics that look like Parkinson's disease.
Speaker:In fact, yesterday, one of my patients that I saw who's now in her 80s had been
Speaker:told very confidently by the movement disorder clinic at Westmead 20 years ago,
Speaker:and then by another very learned neurologist 10 years ago that she had Parkinson's
Speaker:disease, and she doesn't.
Speaker:She's got essential tremor. So we stopped all of her Parkinson's therapy,
Speaker:put her on some beta blockers, and she can now do everything.
Speaker:Parkinson's disease has doubled in our society since I started working as a junior doctor.
Speaker:We have a very good idea of how many patients have Parkinson's disease from PBS data.
Speaker:So in 1998, there were 60,000 Australians on dopamine replacement therapy for Parkinson's disease.
Speaker:Now, that may be a little bit rubbery because sometimes people are on medicines
Speaker:and they don't have Parkinson's disease. And sometimes people have Parkinson's
Speaker:disease and they're not on therapy.
Speaker:Last year, it's 130,000 Australians. Double.
Speaker:Male to female, two to one. Two to one.
Speaker:There is no accurate incidence or prevalence study of Parkinson's disease in Australia.
Speaker:Parkinson's disease in Australia is very rarely genetic.
Speaker:So, there are genetic causes of Parkinson's disease.
Speaker:In the mid-1990s, alpha-synuclein genetic abnormalities were first identified
Speaker:with mutations, duplications, triplications, and that causes autosomal dominant
Speaker:Parkinson's disease, and it's pretty bad Parkinson's disease.
Speaker:Subsequent to that, LRRK2 was identified, and LRRK2 is much more common in some
Speaker:parts of our society, like the Ashkenazic population or the Basque population
Speaker:in northern Spain and some parts of northern Africa.
Speaker:But Parkinson's disease is an environmental disease.
Speaker:It's what we're doing to ourselves. In some jurisdictions, Parkinson's disease
Speaker:is recognized as an occupational disease.
Speaker:In Germany, if you develop Parkinson's disease and you're a farmer,
Speaker:that is a compensable condition from your occupation.
Speaker:In Australia, we have big regional variants of Parkinson's disease.
Speaker:Around Orange and the Central West, Parkinson's disease is incredibly common.
Speaker:It's more common in the wine industry, where the use of fungicides is common.
Speaker:You can go to Bunnings or any farm supply store and buy tomato dust.
Speaker:In tomato dust, there's an agent called rotanone.
Speaker:Rotanone is a mitochondrial poison that is strongly associated with Parkinson's disease.
Speaker:There are very well-known neurologists, Bas Blom, in the Netherlands,
Speaker:who advocates that his patients with Parkinson's disease get rid of all solvents,
Speaker:industrial chemicals, pesticides, insecticides, herbicides, fungicides, out of the home.
Speaker:In 1990, the Netherlands banned
Speaker:a lot of chemicals that we still use in agriculture here in Australia.
Speaker:The Netherlands is the only European country where the incidence of Parkinson's disease is decreasing.
Speaker:Why is that important? Well, cause informs mechanism. Mechanism informs therapy.
Speaker:And unfortunately, unlike the amyloid-based therapies that James and Alice have
Speaker:in the clinic, we don't have anything yet that slows Parkinson's disease.
Speaker:We were the only site of the Parkinson's Progression Marker Initiative from
Speaker:the Michael Jay Fox, which is a big 20, 30-year study looking at the factors
Speaker:that determine the progression of Parkinson's disease. It's still not sorted out.
Speaker:What do we do in the clinic? How do we assess patients? I look after Maddie and I.
Speaker:Poor old Maddie has had the misfortune of working with me for 27 years.
Speaker:She needs a medal. Thank you.
Speaker:I couldn't look after 800 people with Parkinson's disease without Maddie's expertise.
Speaker:Similarly, I have a tremendous CNC, Jing Li, who helps me with our 250 patients
Speaker:with motor neurone disease.
Speaker:So the nursing input isn't valued.
Speaker:It's not remunerated, but it's invaluable to me and to our patients.
Speaker:So all of the stuff that Maddie was talking about, the aged care and the NDIS
Speaker:stuff, she does all of that.
Speaker:And we absorb that cost in neurology, but she spends hours and hours and hours
Speaker:on this pitched battle with these government agencies.
Speaker:She sort of played it down a little bit, but it is battle.
Speaker:So what do we do in clinic?
Speaker:Well, I look after 800 people with Parkinson's disease. They still come to me
Speaker:from all around the place.
Speaker:And it's quite amazing that some patients who've been on therapy for Parkinson's
Speaker:disease for four, five, six, seven years have never had an MRI scan.
Speaker:I have a unique gift for profanity, but I'm not going to swear.
Speaker:But it is quite amazing that if you've got a disease like Parkinson's disease
Speaker:and the initial neurologist doesn't do a scan, because sometimes neurologists think,
Speaker:well, why do I need to do a scan? This is Parkinson's disease.
Speaker:I don't need to do a scan. Well, you do need to do a scan because there are
Speaker:lookalike conditions like normal pressure hydrocephalus, PSP,
Speaker:multiple system atrophy, all these sorts of things.
Speaker:So take a history, careful history, comorbidities, examine thoroughly.
Speaker:There's a very gross staging system of Parkinson's disease,
Speaker:called the Honan-Yah staging, and that's very gross.
Speaker:So stage one is one side, stage two is two sides, stage three is that you're
Speaker:starting to get impairment of balance, stage four is that you can't stand up,
Speaker:and stage five is that you can't sit up.
Speaker:So it's pretty gross.
Speaker:We assess patients, there's a concept in Parkinson's disease called the magic 30 seconds.
Speaker:So I walk out to the waiting room, I greet the patient in the waiting room,
Speaker:because Because I'm a nasty person, my clinic room is the furthest from the waiting room.
Speaker:So I get my 10,000 steps in every day.
Speaker:Greeting the patient, greeting their partner, greeting their family,
Speaker:watching them stand up, shaking their hand, putting them on the scale,
Speaker:walking down the corridor, engaging in banter.
Speaker:Watching them turn, watching them sit down. That's all assessment. And it's magic.
Speaker:We check blood pressure. We weigh patients every time they come in because in
Speaker:Parkinson's disease, you lose weight. You're in negative nitrogen balance.
Speaker:It's very uncommon to see a fat person with Parkinson's disease. It does happen.
Speaker:And some of the therapies tickle up your carbohydrate center.
Speaker:But we weigh our patients every time they come in. We take their blood pressure.
Speaker:We go through their medications very carefully.
Speaker:Because sometimes in medicine, things become siloed and patients will go to
Speaker:the cardiologist who puts them on beta blockers, which are not so great in Parkinson's
Speaker:disease because they exacerbate orthostatic hypertension,
Speaker:hypotension.
Speaker:So we go through all their medicines.
Speaker:We ask them about their vitamins, their supplements, their wool of bat and eye of newt.
Speaker:Pyridoxine toxicity is something that we often see in clinic Where people are
Speaker:taking way too much nature's own or blackmore's rubbish.
Speaker:So spending time with patients, going through their medication,
Speaker:what are they taking, what times are they taking their medicines,
Speaker:how much are they taking, having sure that the patient is there with their partner to corroborate.
Speaker:And that's also important with some of the therapies. So some of the therapies,
Speaker:particularly the dopamine agonists, can tickle up behavioral changes.
Speaker:So because these drugs talk to other parts of your brain, they can amplify behaviours
Speaker:that may be hidden, like gambling, internet gambling.
Speaker:It's a complete nightmare. Pokies, complete nightmare.
Speaker:Hypersexuality, porn, internet. So you've got to interrogate your patients and
Speaker:do it in a respectful way,
Speaker:but with your antenna out, because when these things come out,
Speaker:they can destroy families.
Speaker:So being careful about the medicines and the doses that you use and talking about adverse effects.
Speaker:Therapy. The cornerstone of therapy is levodopa.
Speaker:I use levodopa as the first agent.
Speaker:That's not necessarily the practice around Sydney or Australia.
Speaker:Often they'll start with other therapies like monoamine oxidase,
Speaker:B inhibitors or dopamine agonists.
Speaker:I use levodopa because when people are symptomatic, we need to use the cheapest,
Speaker:best, most effective therapy to reduce symptoms to the lowest level possible.
Speaker:That's what you're trying to do.
Speaker:There is longitudinal data that suggests that the better you treat patients,
Speaker:you may help to slow the progression of Parkinson's disease.
Speaker:That's a little bit controversial.
Speaker:But you need to think about weight and gender. So if you have a 45-kilo,
Speaker:70-year-old woman with Parkinson's disease, you're not going to use the same
Speaker:starting dose as you're going to use in a 130-kilo,
Speaker:50-year-old man.
Speaker:So I had a 135-kilo fellow come to me a couple of years ago who his first neurologist
Speaker:had him on Matapar 62.5, one, three times a day.
Speaker:Homeopathic, did nothing. And he said, the medicine's not working.
Speaker:And I said, well, it's not going to work.
Speaker:It's weight-based. So you've got to give an appropriate dose for the person and their gender.
Speaker:I tend to use principally only Levodopa, either Cinemet or Matapar.
Speaker:And my preference is to use controlled release Cinemet.
Speaker:Again, theoretically, the more
Speaker:fluctuating you are with your levodopa in your blood and in your brain,
Speaker:the worse you prime dyskinesia, where you see patients wriggling.
Speaker:And curiously, we still don't understand why most dyskinesia in women starts
Speaker:in their legs. You'll see them sitting there, one foot will be going.
Speaker:And in men, it's mostly cranioservical. We don't understand that gender difference yet.
Speaker:I often use very low-dose dopamine agonists, often in the form of Cifrol or Nupro, the patch.
Speaker:And then look to adjunct therapies like monoamine oxidase B inhibitors like
Speaker:Zadago, Cifinamide, or Risagiline, Azalect.
Speaker:And then we have a couple of choices with catechol-O-methyltransferase inhibitors
Speaker:with Comtan and Apicapone.
Speaker:So I look at those as adjuncts they help your body to retain dopamine we also
Speaker:need to think about other things that we might need to treat so depression anxiety is a common thing,
Speaker:in Parkinson's disease so if we need to jump in and treat that,
Speaker:But my preference, again, often is to use SSRIs rather than SNRIs,
Speaker:because, again, without,
Speaker:objective data to back it up, the SNRIs often turn up anxiety,
Speaker:whereas SSRIs don't.
Speaker:Constipation is universal. It is a movement disorder, pardon the pun.
Speaker:But we approach that very simply.
Speaker:Two minutes, I've got two minutes, goodness.
Speaker:Fluid, you've got to have enough fluid. So I ask patients, what does your poo look like?
Speaker:Is it rabbit pellets? Is it Maltesers?
Speaker:If it's rabbit pellets or Maltesers, you don't have enough water because your
Speaker:bowel slows down and it sucks fluid out of your poo.
Speaker:So we use movacol, we use some form of senna like Nulax.
Speaker:I happen to like Nulax, but it doesn't really matter.
Speaker:And so it's very simple, enough water, movacol, constipation.
Speaker:And again, you have to ask because patients won't necessarily volunteer it.
Speaker:Okay management is not just
Speaker:about pharmacotherapy so very early on we talk about only dead fish float with
Speaker:the stream so getting patients to stay engaged involved active whatever that
Speaker:is you got to ask people to do exercise according to what their preference is,
Speaker:So sending my 135-kilo truck driver to Tai Chi and,
Speaker:or Pilates, that's just not going to work. So you send him to,
Speaker:you know, knock out Parkinson's disease, the punching guys.
Speaker:So you've got to tailor exercise and you try and get patients to do at least
Speaker:30 minutes of good going exercise a day.
Speaker:There are some clinics and Maddie mentioned them.
Speaker:So there's the various clinics that espouse a very active approach to Parkinson's disease.
Speaker:And they're all really good. They're not for everyone. You've got to tailor it to the person.
Speaker:It's got to be patient-centric in the context of their family,
Speaker:so listen to what your patients are telling you.
Speaker:Make sure that I try to get patients to come with their partner because that's
Speaker:when you can really interrogate what's going on because someone's sitting next to them going, oh, yes.
Speaker:So listening to what's going on in the clinic.
Speaker:I have a few disclosures. NHMRC, MRFF, Shake It Up, and Michael J. Fox Foundation.
Speaker:I sit on the scientific advisory board for Selozia, which is a startup here at Macquarie.
Speaker:I have done some contract work for Biogen around therapy in motor neurone disease,
Speaker:and I'm a full-time employee of Macquarie University.
Speaker:Parkinson's is very common. It's more men than women, no two identical.
Speaker:And we'll circulate the slides. You don't have to photograph them.
Speaker:I'm happy for these to come to you all.
Speaker:We need to consider advanced therapies. I haven't even touched on advanced therapies,
Speaker:because that's a day in and of itself and maybe we can do that at some stage
Speaker:because hopefully next year we'll be starting up DBS here at Deep Brain Stimulation
Speaker:Surgery here at Macquarie and we already do some of the advanced therapies that
Speaker:you might have seen on Channel 9 the Fos levodopa.
Speaker:But why give something by a pump when a tablet works just as well?
Speaker:I'd like to thank you all for coming on a Saturday morning, giving up your time,
Speaker:because it really is fantastic to see faces of people that I have a correspondence
Speaker:with about patients that I've looked after. So thanks for coming.
