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I'm Dr. Fernando Pagan, I'm a movement disorder neurologist
at MedStar Georgetown University Hospital.
I see patients with movement disorders which the most common movement disorder
is Parkinson's Disease. So Parkinson's patients,
patients who have disorders similar to Parkinson's Disease,
patients with tremors, abnormal muscle spasms or dystonia,
patients with ticks or Turret's Syndrome
and patients with cerebelLar problems that lead to abnormal gaits like ataxia.
So these are the types of patients that we see in our movement disorder clinic
here at MedStar Georgetown University Hospital.
I really like my job because we really can make a difference.
Neurology has really turned into a field where
we can really be hands on and intervene and modify diseases
and improve quality of lives.
We're actually changing patients' lives now in neurology,
and I really see that when I get to see a patient come in
who is in a wheelchair and the next visit they're walking.
That's pretty amazing.
One of the reasons to come to MedStar Georgetown University Hospital,
especially in the movement disorder center,
we are a national Parkinson's Foundation Center,
we're taking care of the whole entire person, we don't only look at the tremor,
we don't only look at the stiffness of a person,
or the slowness that they're having from the disease.
We really take a look at the whole person,
we look at medication, alternative treatments,
we also look at physical therapy, speech therapy,
we really try to find every singe type of treatment possible
even surgical intervention to help improve the quality of life.
What's unique about MedStar Georgetown University Hospital's
Deep Brain Stimulation program is that the whole entire team
is present in our facility to be able to help improve the quality of life.
In order for DBS to be successful
you need a very skillful nurse surgeon,
you need a neurologist to refer you to make sure
that you do have Parkinson's Disease,
a neuropsychological testing as well to make sure
that the cognition is in tact,
and then you need the follow-up
to readjust the medications
and adjust the deep brain stimulator,
and then the ultimate piece is the physical therapy specifically for Parkinson's Disease
as we adjust the stimulators and adjust the medication.
So neurosurgery and neurology working together in the same facility
I think enhances the quality of life for our Parkinson's patients,
and that is unique to Georgetown University Hospital.
Research is also an important part of our clinics here
at Georgetown University Hospital.
MedStar is committed to excellent care and that really does
also include research, we have a lot of clinical research programs.
We're looking to see how we can enhance the quality of life for our patients,
not only today, but in the future.
Sometimes we have certain treatments that are only available
in the clinical research side and will soon be available
in the clinical world. For example, over the last couple of years
we've had patients who had been getting the Neupro, Rotigotine patch,
which was only available in research clinical trials
and it will be finally available here in the United States.
So our patients have already had that exposure
and been able to have an improvement in their quality of life
before it was available clinically.
One of the other things that we're looking at very intensively in research is
looking at new ways to deliver medications, so we not only do...
we have Deep Brain Stimulation to enhance the quality of life,
but we have new drug delivery systems or pumps
to deliver the medicines continuously throughout the day.
And that... we do and have offered that to some of our patients
in clinical trials.
And so we're changing the way that medications are delivered
or changing the way we're going to have therapeutics
for our patients in the future.
Parkinson's Disease is defined as a motor disease.
It's based on motor symptoms that we can see in individuals.
For example, slowness in movement, so they're not moving
as quickly as they were before is one of the diagnostic criteria.
Another diagnostic criteria is something called rigidity or stiffness of muscles.
And the last one of the triad is tremor. It's usually a rest tremor.
About 70% of Parkinson's patients will have rest tremor.
So that means 30% will not. So the one criteria that has to be present
is that there is slowness in movement or bradykinesia.
So bradykinesia, the slowness in movement, rigidity and tremor
is what we classically use to diagnose Parkinson's Disease.
It's a clinical diagnosis. In other words,
we see the symptoms and how the patient will ultimately
respond to the medications will ultimately tell us
whether somebody has Parkinson's Disease or not.
One of the things that we're learning about, that there is a lot
of non-motor features about Parkinson's,
so patients can not only have motor symptoms, they can have other problems.
So constipation for example can precede the motor symptoms
by almost a decade. REM behavioral sleep disorder or sleep problems
can also precede the diagnosis by several years as well.
Anxiety, depression, problems with smell identification,
so we're also learning that Parkinson's Disease is much more
than a motor disorder, it also has a lot of non-motor issues as well.
I believe that we will redefine Parkinson's probably within the next several years
because we're learning that at the time that we actually diagnose Parkinson's Disease
there has been a loss of about 60%-80% of all the neurons
that produce dopamine, and that's what causes the symptoms of Parkinson's,
that if you're not producing a chemical in the brain called dopamine,
you start to develop slowness in your movement, rigidity
and possibly a tremor. So by the time we've made a diagnosis,
we have already seen this degeneration occur and what we're learning is
that when you've lost somewhere between 40%-50%,
that's where the non-motor symptoms are present.
So over the next decade or so we're going to have to push the envelope
into making the diagnosis before the motor symptoms are there
so that we can start to intervene and potentially slow down
or stop the progression.
We make the diagnosis of Parkinson's based on the clinical symptoms.
Usually another physician or family member or friend
have noticed that somebody is no longer moving one arm
as well as the other, so the arm movement is decreased
or they've developed rest tremor
or their handwriting has gotten a little smaller,
they're waking up with a lot of early morning stiffness,
they're having a stooped posture,
so those are the symptoms that usually bring a patient over to a neurologist.
Again, the motor symptoms are the ones that usually come to a neurologist.
Sometimes a patient has been having some vague symptoms for a while,
difficulty with sleep, constipation, muscle cramping,
and they may have been complaining to their primary care physician
for several months or several years
and they've never really been able to figure it out,
but once you start to see the muscle stiffness and the tremor,
that's when we usually see them in neurology.
We make the diagnosis based on the clinical exam,
we do a full neurological workup, a lot of time we may
or may not get an MRI, the MRI usually is normal
and nowadays we can even, for some patients that were kind of on the fence
or there may be some typical features that we may need
some confirmation based on our clinical exam,
we can order a scan, it's called a DATScan, which is a beta-CIT scan.
It's type of like a PET imaging or positron emission tomography,
it has some similarities to it,
very similar to what we'll do for patients with Alzheimer's
or even some of the neoplastic disorders like cancer,
we can get a brain imaging to tell us about the content
or how many dopaminergic neurons there are in the area of the brain
called the basal ganglia, which is very important
in the path of physiology and Parkinson's, so we can actually do
a nuclear medicine scan to help us with the diagnosis
or confirm for some patients.
So we have a lot of different medications available for Parkinson's Disease.
The gold standard continues to be Levodopa. That's a precursor for dopamine.
Parkinson's Disease is based on motor symptoms that are caused
by a deficiency in the neurotransmitter dopamine.
So anything that we use to enhance dopamine
can be very beneficial for Parkinson's.
The gold standard again is a medicine that combines Levodopa
with a drug to prevent side effects called Carbidopa,
Sinemet is a trade name for that one. So that's kind of the gold standard,
but what we're learning is the amount of Carbidopa, Levodopa
or Sinemet that you use can lead to complications later on,
so using the minimum amount to give the best quality of life
and potentially more continuous drug delivery of this compound
rather than a very pulsatile dosing is what seems
to be best for patients, right now we're learning.
When to use Levodopa is where the question really is.
When you see a patient with very mild symptoms,
sometimes we can get by without using Levodopa first.
Although it's the most potent, you can use other drugs.
For example, you can use Monoamine oxidase B inhibitor,
one of the most common ones that we'll use is called Rasagiline or Azilect.
This medication stops the breakdown of dopamine, so that your body can recycle
or reuse the dopamine that you've made naturally
and sometimes that can help improve the quality of life
rather than using no medication whatsoever.
So for a very mild patient, this is a great drug to start off,
very well tolerated. If the patient has a little bit more symptoms,
you can use something like a dopamine agonist.
The most common dopamine agonists that we have are Pramipexole and Ropinirole
are the main ones, we even have one a day formulations again to have
more drug delivery, and very soon we're going to have a patch
called Rotigotine or the Neupro patch that also will deliver the drug
nice and continuously.
You see this theme of having... drugs are now once a day
and more continuously delivered, and I think this is going to equate
to better quality of life, and we're learning that by giving the medications this way
not only do we help enhance some of the motor symptoms of Parkinson's,
but the non-motor symptoms as well.
So that's really very fascinating what we're seeing with this new type of drug delivery.
This is something that's clearly new now in this decade that wasn't available previously.
As the disease progresses, sometimes we have to be a little bit more aggressive.
Sometimes we'll use a combination of certain medications to enhance Levodopa.
For example we can use a COMT inhibitor as well that also helps prevent
the early breakdown of Levodopa so more of it gets up into the brain,
we can use older medications like Amantadine, the trade name is Symmetrel.
This medicine helps release dopamine and if a patient has developed dyskinesias
or motor fluctuations, this can help with these types of symptoms as well.
But once we start to get into the motor fluctuations,
that's where we can potentially consider other treatments
that are a little bit more invasive but could improve quality of life significantly.
The main one right now that's FDA approved here in the United States right now
is the Deep Brain Stimulator.
I often get asked that question, is Parkinson's curable?
Right now the way that I'd like to look at it is we can modify the disease,
we improve patients' quality of life dramatically.
We can get a patient with proper medicines in Parkinson's Disease
to feel like they don't have a disorder so that they can continue
to live their daily life and enjoy the quality of life,
be able to attend family functions. In the future,
hopefully we will find treatments that not only slow down
but stop the progression of Parkinson's,
and I think that's where gene therapies stem-cell research are headed.
Gene therapies I think have the best hope to stop the progression of Parkinson's
and then stem-cells could replace the loss of dopaminergic neurons that we had.
So stem-cells are a replacement and gene therapies would stop
the progression, and I think we need those two together
to ultimately come up with a cure.
Right now a patient without treatment in Parkinson's clearly progresses
much quicker than a patient with treatment. So treatments do modify.
In fact, take a look at the history of Parkinson's Disease, before 1970
patients with Parkinson's Disease expired or died much earlier
than that of the general population's. Since 1970,
since we've had treatments available for Parkinson's Disease,
Parkinson's patients are living just as long as that of the rest of the population
but what we need to do is we need to improve their quality of life
with these medications, so they're living longer but we have to give
better medicines, better drug delivery systems
to improve the quality of life as well.
Deep Brain Stimulation is a treatment that can be considered
when we start to see our patients start to have the motor fluctuations
or their tremors are not controlled by the medications.
There's a small subset of the population that the tremor is resistant
to our best drugs like Carbidopa and Levodopa.
There, Deep Brain Stimulation is better than the medication.
In general, Deep Brain Stimulation gives you the same effect
that our medicines like Carbidopa or Levodopa give you
but for longer periods of time. So if we have a patient
that's starting to fluctuate, they're wearing off,
they're having difficulty taking so many medications throughout the day,
this is the ideal patient for Deep Brain Stimulation.
So Deep Brain Stimulation is a pacemaker...
is a pacemaker device but instead of being inserted into the heart,
it's inserted into the brain.
We have two areas in the brain that we use for Parkinson's Disease
that we can put these electrodes in. One of them is called the STN
that's short for "sub-thalamic nucleus",
the other one is called GPI or "globus pallidus interna".
These are a set of nuclea on the basal ganglia.
When you have a dopamine deficiency there's an over-stimulation coming
out of those two areas. What we do is we put in an electrode there
and we over-stimulate, we drown out that over-stimulation coming out.
We're actually mimicking the same effect that Carbidopa and Levodopa does.
When you give a Parkinson's patient Carbidopa or Levodopa,
that over-stimulation that's causing the stiffness, the rigidity and the tremor
resolves, because that stimulation that is over active,
now the medicine brings it down. Now, with the Deep Brain Stimulator,
we can mimic the effect of Carbidopa, Levodopa or Sinemet.
I like to call it "electrical Sinemet", because it does the same thing as Sinemet
but just in that localized area, so you can put the electrode there
into that nucleus and start stimulating there and drown it out
so the patient's tremor can go away
and their rigidity and stiffness can go away,
they can move their fingers much quicker, they walk faster,
their arm movement returns,
so the motor symptoms with Deep Brain Stimulation are improved dramatically
and the right type of patient is the type of patient who is responsive to the medicine
but is having more of these motor complications or motor fluctuations.
After the Deep Brain Stimulators are inserted
we usually wait about 4 weeks before we actually turn it on
because a lot of times there's a little swelling around the electrode
and some patients get benefit already just after placing the electrode.
We can do our best program after those 4 weeks.
At that 4-week mark we turn on the stimulators for the first time
and we begin to start adjusting the medications.
Usually we can reduce the Carbidopa/Levodopa about 30%-60%
depending on the patient. And then, we usually see our patients
about ever 4-6 weeks for the next 3-4 months
to really fine-tune the medications as well as the Deep Brain Stimulators.
We want to enhance the quality of life for our patients,
we know it's going to take time, it doesn't happen right away.
A lot of times immediately a patient feels better,
when we've turned it on they no longer have tremor,
but we do need to follow those patients to optimize.
We want to use the minimum amount of medicine
and the right amount of stimulation
so that we don't cause side-effect and we improve the quality of life.
In general we can improve the on-time, that's the amount of medication,
when the medicine is working about 4-6 hours in a Parkinson's patient
after Deep Brain Stimulation. The best that I can do
as a movement disorder neurologist by adding another medication
is about 1-2 hours at most, so there's a huge difference in quality of life
but it's a process.
In the past, 10 years ago, we'd have to put one pulse generator on each side.
So now we have one that controls for both sides
and it's also gotten smaller over that time.
We also have a rechargeable one that we can actually recharge
through the skin and that can last up to 10 years.
As a programmer I have seen that I have a lot more ability to give to my patients.
For example, I can adjust or give certain groups to my patients,
depending on what they're doing.
I have certain settings for my patients nowadays
for when they're talking on the phone versus when they're just walking
or riding their bicycle or competing.
So one of my... for example,
I have one patient that he will use group A for his normal activities,
when he goes to work he'll use group B, if he's on the phone he'll use group C,
but when he's competing in... he does some competition with bike riding,
he'll be on group D. He can't talk, but he can peddle like the wind.
So you can really tailor a specific therapy depending on the patient.
When we first started doing this we had about 12,000 options for programming.
Now we have over 22 million options to really fine-tune that program
and to get the best quality of life for our Parkinson's patient.
What that's meant is there's probably less re-positioning of electrodes
that there used to be, because we can find something in between
to improve the quality of life for our patient,
so there have been significant advances in the pulse generation,
the pulse generators, in other words, the pace-maker
of the Deep Brain Stimulator over the last several years.
I think there'll be... continue to be advancements over the years.
When we used to give a patient access reviews so a patient could just tell
whether they were on and off, it was just a couple of lights
and a couple of beeps that they would hear. Now it's a whole entire LCD screen.
They have almost like a little mini programmer, like I have,
and I can give them ranges so they can adjust themselves if they want to
or if they need to, and they can choose. It actually tells you what group you're in,
A,B,C, or D. Again, I have some patients who are just in group A,
but I have patients that I give them 4 different groups
and I can stimulate them 4 different ways, depending on what they're doing.
So the future of Parkinson's the way that I see it is
we're going to see better medications
and we're going to see better ways to deliver the medication
for symptomatic improvement.
And then we're going to see treatments like gene therapies or stem-cells
to stop the progression of Parkinson's or replace the neurons that we've lost.
In gene therapies, where I see some improvements coming, are...
we've seen some gene therapy trials where you use a viral vector injected into the brain
to increase GABA. Most of the time when we're talking about Parkinson's
we're taking dopamine. There's other neurotransmitters involved,
they used a viral vector with something called Glutamic Acid Decarboxylase
or GAD for short, then when they put the GAD there
patients who got the real surgery versus the sham surgery,
they improved in their motor symptoms. So there may be other ways
to treat Parkinson's than just delivering dopamine itself.
But we'll see trials within this decade not only for GAD
but also nerve growth factors
and even other enzymes to enhance dopamine production,
and the hope is to be able to develop a gene to stop the deposition
of the abnormal protein called alphaSYN nuclei
that we see deposited in brains of patients with Parkinson's Disease.
Very similar to what we hear that's going on with Alzheimer's
but with Alzheimer's its beta-amyloid,
so I do see a significant future there with the gene therapies
but we need further research.
The DATScan is a new nuclear imaging test that we can use
to help us with the diagnosis of Parkinson's or Parkinson's related disorders.
It doesn't differentiate between Parkinson's Disease and Parkinson's related disorder
but it can definitely tell us that there's been a loss
in the amount of dopaminergic neurons.
But there's other areas that I think the DATScan can be helpful
in the management of Parkinson's. It's going to continue to evolve,
we're still at the very early stages but it can be a very useful tool
for us neurologists and also for the patient
to help him identify this disease and that is also available here
at MedStar Georgetown University Hospital.