1. Parkinson’s Disease Mariecken V. Fowler, M.D.
Winchester Neurological Consultants
Board Certified in : Neurology,
Behavioral Neurology and Neuropsychiatry,
and in Neuroimaging 1

2. What is Parkinson’s disease?
Parkinson’s disease (PD) is a chronic, progressive disease in which ordinary movement and other symptoms may worsen over time
1817: James Parkinson “An Essay on the Shaking Palsy”
Diagnosis requires 2 of 3:
Bradykinesia
Rigidity
Tremor (primarily at rest)
Onset insidious, unilateral  bilateral
So, first…what exactly is Parkinson’s disease? Named for James Parkinson, the physician who first identified its collection of symptoms, Parkinson’s disease is a chronic, progressive disease in which ordinary movement becomes more difficult over time. PD is a neurological disease, meaning its symptoms may worsen over time.
Some of the difficulties you may have been having—and what may have gotten you to see a doctor—may be things like feeling like you’re slowing down, experiencing a slight tremor in your hand, or having some stiffness as you move around.
PD is chronic, which means right now we don’t have a cure that can make it go away. And it is progressive, meaning the symptoms you’re experiencing now will worsen as the disease progresses.

3. Parkinson’s Disease Prevalence
Approximately 1 million people in the US have PD1
More people have PD than have multiple sclerosis, muscular dystrophy, and Lou Gehrig’s disease combined1
Average age of onset is around age 622
Younger people can get PD (called young onset PD), but it is less common3
And if you have PD, you’re not alone. Right now we estimate about 1 million people in the US are living with PD—which is more than many other neurological diseases combined.
It is considered an older person’s disease because the average age of onset is about 62. When younger people get the disease (age 40 and under), we refer to that as young onset PD. Young onset PD is far less common than the classic disease.
Statistics on Parkinson’s. Parkinson’s Disease Foundation. Available at
Young onset diagnosis. Parkinson's Disease Foundation. Available at
American Parkinson’s Disease Association. National Young Onset Center. Available at

4. Famous people with PD, past and present
Michael J. Fox
Janet Reno
Muhammad Ali
Sir Michael Redgrave
Pope John Paul II
Vincent Price
Deborah Kerr
Eugene McCarthy
And you’re in good company with PD…many famous people have had PD.
Wikipedia. List of Parkinson’s disease patients. Available at

5. Cause of PD still not known
Experts believe PD is the result of interaction between genetic and environmental causes1,2
PD is more common in some families than in others
Genes associated with PD have been found but are not thought to play a role in most cases
Exposure to certain pesticides may contribute to the development of PD
So what causes PD? That’s a good question. The truth is we just don’t know exactly. Researchers now believe there’s a combination of genetic predisposition and environmental factors at work. They’ve found that PD does run in some families, and they have found certain genes associated with the disease. But exactly how those genes affect the development of the disease isn’t known.
Research has also shown that people exposed to significant amounts of pesticides (like farm workers) may have an increased risk of PD, so that’s why they think environment does play a role.
Causes. Parkinson’s Disease Foundation. Available at
Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006.

6. Primary movement symptoms
4 major movement (motor) symptoms1,2
First 3 are most common in early PD and usually appear on one side of the body1,2
Everyone experiences symptoms differently
Resting tremor
Slowness (bradykinesia)
Stiffness (rigidity)
Poor balance
PD is classified as a movement disorder because its hallmark symptoms are movement related. You may have experienced some of this already—tremor in one of your hands or legs while you’re at rest, slowness, also called bradykinesia, stiffness, and even poor balance.
It’s important to understand that PD is a very individual disease, so your symptoms may be quite different than the symptoms of the person sitting next to you. So as you learn more about Parkinson’s, it’s important that you don’t compare yourself to others and assume that you’ll experience the same symptoms they do down the road.
Symptoms. Parkinson’s Disease Foundation. Available at
Jankovic J, In. Pahwa et al, eds. Handbook of Parkinson’s Disease. 3rd ed. NY, NY. Marcel Dekker, Inc.;2003.

7. Other symptoms Movement (motor) 1,2 Stooped posture Small handwriting
Decreased arm swing
Cramping
Difficulty swallowing
Changes in facial expression
Shuffling
Sexual dysfunction
Nonmovement (nonmotor) 1,2
Depression, apathy, or anxiety
Sleep problems
Pain
Slowed thinking
Memory difficulty
Constipation
Urinary problems
Fatigue
Reduced sense of smell
Loss of appetite
As we do more and more research on PD, we learn that it is a disease of many symptoms, and that it includes many nonmovement (or nonmotor) features. Nonmotor symptoms can include depression, sleep trouble, pain, loss of sense of smell, constipation, and more.
It’s important that if you experience any of these symptoms—or anything that’s new or unusual—tell your physician. Even if you don’t think these symptoms are related to your PD, it’s important that your doctor know about them so he or she can help you treat them.
Symptoms. Parkinson’s Disease Foundation. Available at
Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

8. The pathology of PD neuron dopamine
Neurons transmit messages to other neurons via chemical messengers, or neurotransmitters1,2
One of the neurotransmitters that helps control movement is dopamine1,2
In PD, neurons lose the ability to make and transmit dopamine1,2
Loss of dopamine leads to difficulty controlling movement1,2
neuron
dopamine
So let’s take a look at what’s happening in the brain that leads to these motor and nonmotor symptoms.
In the brain, cells called neurons transmit messages to other neurons via chemical messengers called neurotransmitters. One of the neurotransmitters that carries messages to the parts of the brain that control movement is called dopamine.
In PD, the neurons that produce dopamine begin to die, losing their ability to make dopamine. Therefore, the amount of dopamine in the brain decreases, so these messages telling the body to move start to go slower and take longer. The result is that you have more difficulty controlling ordinary movements.
What is Parkinson's disease (PD)? National Parkinson Foundation. Available at
What is Parkinson's disease? Parkinson's Disease Foundation. Available at

9. An evolving picture of PD
PD begins in the mid-brain, in the substantia nigra
substantia nigra
Now, traditionally, PD has been considered a disease that begins in an area of the brain called the substantia nigra, a region with lots of dopamine-producing cells. That’s because the classic symptoms are the movement or motor symptoms we see in the early part of the disease.
Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

10. Pathology of PD Neurodegenerative
↓Dopamine-containing neurons in substantia
nigra
Imbalance between dopaminergic outflow
tracts in the basal ganglia causes the symptoms
Lewy bodies
Spherical hyalin masses
Present in most but not
all forms of PD 10

11. An evolving picture of PD
Adapted with permission from author (Braak H), taken from Braak H, Ghebremedhin E, Rub N, et al. Stages in the development of Parkinson’s disease–related pathology. Cell Tissue Res. 2004; 318:
A current hypothesis, called the Braak hypothesis, suggests PD begins long before movement symptoms appear1
PD begins in the lower brainstem and progresses to other parts of the brain1
Some nonmotor symptoms appear before diagnosis1
A more recent theory, however, leads us to believe that Parkinson’s begins much earlier than we thought, and not in the substantia nigra. In fact, we believe now that it begins in the brainstem and only after a few years progresses to the substantia nigra where it really starts to affect movement.
Why this is important is that we’re starting to identify some nonmotor symptoms that appear before the motor symptoms do—you may have in fact experienced some of these without even realizing it. Many PD patients experience a loss of their sense of smell, or have difficulty sleeping, or even experience constipation years before the classic PD symptoms appear.
What we’re hoping is that we can begin to identify these very early signs of PD, so we can get patients diagnosed earlier and begin appropriate treatment earlier.
Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

12. Putting PD treatment together
You may have heard about or read about some of the medications we use to treat PD—and I’ll talk about those in a minute—but I wanted to make the point that there are other important aspects of your health that can positively impact your Parkinson’s.
So along with medication, we’re going to talk about how exercise, nutrition, and even mind/body activities (like meditation) can help you manage PD.

13. Your PD treatment team
Another thing to consider is that your treatment team is more than just your physician. A comprehensive care approach can help you not only treat your symptoms, but also help you maintain your independence and reduce disability. Different members of the team concentrate on different aspects of treatment to give you a well-rounded approach.
You may have already been referred to or seen a neurologist, a specialist who treats PD. PD is a complicated disorder with many symptoms that vary from person to person. So if you are not currently seeing a specialist, you should talk to your primary care physician or other people you know with PD about getting a referral.
The nurse in your neurologist’s office can also be very helpful in terms of providing information and helping you cope with some of the challenges of PD. And although your doctor will direct your treatment, your nurse can be a good resource for you along the way.
A physical therapist can work with you to improve strength, endurance, movement control, flexibility, and more. They can customize an exercise program that you can do at home to improve your mobility.
An occupational therapist can help you with advice on how to manage daily activities when they become more difficult. They can help you set up your work environment, and even help you find ways to manage those day-to-day chores at home.
And finally, your primary care physician should receive copies of any tests and treatments you receive, as well as stay in communication with your other doctors.

14. How PD medications work
Levodopa replaces dopamine
COMT-inhibitors preserve levodopa
MAO-B inhibitors preserve existing dopamine
We’ll talk about 4 basic categories of medications today, and this illustration shows how they work.
What you’re looking at is an illustration of 2 neurons and dopamine (the “D’s”). Each of these medications somehow works or interacts with dopamine, helping to support dopamine levels in your brain.
The medications we’ll talk about today are MAO-B inhibitors, dopamine agonists, levodopa, and COMT inhibitors.
Dopamine agonists mimic dopamine
Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006.
Medications for motor symptoms of PD. National Parkinson Foundation. Available at

15. Levodopa replaces dopamine
Levodopa / Sinemet
Converts to dopamine once it enters the brain1
Most effective drug to treat symptoms2
However, new symptoms (called motor complications) emerge over time2
Levodopa replaces dopamine
Levodopa is probably the one medication you may have heard of—Sinemet is the brand name when combined with carbidopa. Levodopa works by entering the brain and converting into dopamine, thereby replacing the dopamine your neurons are no longer making.
At this point, levodopa is about the most effective symptomatic drug we have—patients do very well on it. However, the challenge with levodopa is that its effectiveness is somewhat limited. After a few years on levodopa treatment, patients begin to experience new symptoms directly related to the levodopa.
Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006.
Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

16. Motor complications of levodopa
Motor fluctuations occur as levodopa loses its effectiveness
Dyskinesias: uncontrolled, jerky movements
“On” time
When levodopa is controlling PD symptoms
“Off” time
Return of PD symptoms before the next dose of levodopa
These symptoms are called motor complications. The first motor complication we often see is called motor fluctuations—meaning the symptoms fluctuate between being well controlled and not being well controlled.
We call this “on” and “off” time. “On” time is the time when levodopa is working well. “Off” time is when symptoms return before the next dose of levodopa is taken—the levodopa is wearing off before it should. At this point physicians will change the levodopa dose or add other medications to help counteract the wearing off.
Dyskinesias are another motor complication of levodopa. Dyskinesias are uncontrolled movements, often in the arms and legs, that sometimes look like dancing.
Again, these complications don’t occur right away, but after several years of levodopa treatment. For this reason, physicians try to use other medications before going to levodopa—saving the most effective medication for later in the disease.
Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

17. Inhaled carbidopa/levodopa

18. Time- Release Levodopa-Carbidopa
Rytary- FDA approved in Jan 2015
Time released levodopa-carbidopa
Holds medication in microspheres that break down at different rates
Advantages: Improved UPDRS scores, reduced off times. Mean off time reduction from 35% to 24% compared to Stalevo
Disadvantages: Increased number of pills per dosing, conversion to rytary slightly cumbersome

19. Levodopa-Carbidopa Intestinal Gel (Duopa)
Approved by FDA in Jan 2015 for treatment of motor fluctuations with advanced Parkinson’s
Medication in suspension and slowly infused through a tube into the jejunum
Advantages: Continuous therapy which reduces the pulsatile nature of oral levodopa
Disadvantages: expensive and high adverse event rates

20. COMT-inhibitors/ Comtan
Work to prevent the breakdown of levodopa so more dopamine will be available
Always prescribed with levodopa
COMT inhibitors work by preventing the breakdown of levodopa before it gets to the brain—so there’s more levodopa left to convert to more dopamine.
This medicine only works with levodopa, so it’s not prescribed on its own.
COMT-inhibitors preserve levodopa
Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006.

21. Dopamine agonists: Requip, Mirapex, Neupro patch
Mimic the activity of dopamine in the brain—act as the messenger1
Can be used alone in early PD or with other drugs in later PD2
Dopamine agonists mimic dopamine
Dopamine agonists are another category of medication for PD. Dopamine agonists act like dopamine in the brain, taking dopamine’s place as the messenger.
Dopamine agonists also are used by themselves or along with other PD medications.
Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006.
Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

22. Rotigotine Patch ( Neupro)
Transdermal delivery of Dopamine Agonist
Once daily treatment for PD and RLS
May be used in early or advanced disease
Reduces “off-time”
Patches available in 2,4,6,8 mg

23. Apomorphine SQ/ Pump (Apokyn)
Dopamine Agonist used for motor fluctuations and off time
Subcutaneous injection, available in pump but not FDA approved in US
Goal is to reduce amount of off time experienced by patients
Advantage: avoid ups and downs of levodopa
Disadvantage-difficult to use, multiple injections daily, can’t use if intolerant to DA
Apomorphine SL
film was unable to get
FDA approval

24. MAO-B inhibitors: Azilect, selegiline
Work in the brain to prevent the breakdown of dopamine1
One of these can be used alone in early disease and all can be used with other drugs in more advanced disease2
MAO-B inhibitors preserve existing dopamine
Let’s start with MAO-B inhibitors. MAO-B is an enzyme which breaks down the dopamine in your brain. An MAO-B inhibitor blocks that action and prevents dopamine from breaking down. Therefore, more of your brain’s existing dopamine is preserved.
One MAO-B inhibitor can be taken on its own in the early phase of PD, and all can be taken along with other PD drugs as symptoms become more severe.
Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006.
Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

25. Surgical options Surgery is an option for patients :
Symptoms are no longer controlled with medications
Having side effects from medication
Quality of life is suffering
Have fluctuating symptoms throughout the day
Deep brain stimulation (DBS) uses an electrical implant to stimulate targeted areas of the brain and change nerve signals
Now, let’s talk a bit about medical options once medications aren’t helping as much as they need to. There are surgical options for Parkinson’s, reserved for those patients whose symptoms aren’t adequately controlled with medications.
In deep brain stimulation, or DBS, an electrical implant is placed in the brain to deliver electrical impulses to the areas that control movement. This stimulation helps block the abnormal nerve signals that cause the PD symptoms. DBS doesn’t destroy nerve cells or damage healthy brain tissue.
There are other types of surgery in which parts of the brain are actually removed to help reduce PD symptoms. These surgeries, which include thalamotomy, pallidotomy, and subthalamotomy, are rarely done today.
Surgical treatment options. National Parkinson Foundation. Available at

26. Surgical options Surgery may not be for you if:
Significant cognitive changes are present (dementia)
You have uncontrolled depression
You have atypical Parkinson’s
You never had a significant response to medications for Parkinson’s
Your Parkinson’s was caused by other medications (antinausea or psychiatric medications)
Now, let’s talk a bit about medical options once medications aren’t helping as much as they need to. There are surgical options for Parkinson’s, reserved for those patients whose symptoms aren’t adequately controlled with medications.
In deep brain stimulation, or DBS, an electrical implant is placed in the brain to deliver electrical impulses to the areas that control movement. This stimulation helps block the abnormal nerve signals that cause the PD symptoms. DBS doesn’t destroy nerve cells or damage healthy brain tissue.
There are other types of surgery in which parts of the brain are actually removed to help reduce PD symptoms. These surgeries, which include thalamotomy, pallidotomy, and subthalamotomy, are rarely done today.
Surgical treatment options. National Parkinson Foundation. Available at

27. Surgical options- at WMC since 2012
WMC offers new hope for
Parkinson’s disease patients
WINCHESTER, VA — Insertion
of electrodes and a stimulator
into a region of the brain and
in the upper chest, respectfully,
has proven to decrease symptoms
of Parkinson’s disease.
This surgical option for
Parkinson’s disease is now
offered at the Winchester Medical
Center.
Now, let’s talk a bit about medical options once medications aren’t helping as much as they need to. There are surgical options for Parkinson’s, reserved for those patients whose symptoms aren’t adequately controlled with medications.
In deep brain stimulation, or DBS, an electrical implant is placed in the brain to deliver electrical impulses to the areas that control movement. This stimulation helps block the abnormal nerve signals that cause the PD symptoms. DBS doesn’t destroy nerve cells or damage healthy brain tissue.
There are other types of surgery in which parts of the brain are actually removed to help reduce PD symptoms. These surgeries, which include thalamotomy, pallidotomy, and subthalamotomy, are rarely done today.
Key participants in neurosurgical first at Winchester Medical
Center are L-R Mariecken Fowler, MD, neurologist Winchester
Neurological Consultants, Dale Sines, first patient to undergo deep brain stimulation,and Lee Selznick, MD, neuronsurgeon Virginia Brain and Spine Center.
Surgical treatment options. National Parkinson Foundation. Available at

29. Exercise: an important part of therapy
Research shows regular exercise improves:
Tremor
Balance
Gait
Flexibility
Motor coordination
An area that’s getting a lot of attention lately is exercise and its role in PD. Studies have shown that regular exercise improves many of the symptoms patients experience, as you’ll see here. The National Parkinson Foundation has found that regular exercise programs are associated with a greater sense of well-being in Parkinson’s patients.
Exercise. National Parkinson Foundation. Available at

30. A balanced approach to exercise
When you begin an exercise program for PD, first of all, it’s important to consult your physician or a physical therapist. He or she can help you develop a program that incorporates these 4 areas—strength, endurance, balance and coordination, and flexibility. Improving each of these areas has been shown to benefit patients with PD, so it’s a good idea to pay attention to each one.
Exercise. National Parkinson Foundation. Available at

32. Mind and body wellness Other nonmedical aspects of therapy:
Massage to relieve rigidity
Meditation to relieve anxiety
Tai chi to improve balance
Proper sleep for overall health
Hobbies, friends, and support groups for emotional well-being
Mind/body wellness is another important aspect of PD therapy. Massage—when administered by a licensed professional—may help relieve rigidity and other motor symptoms. Meditation can help you relieve anxiety, and enrolling in a tai chi class can actually help you improve your balance and flexibility.
One aspect of therapy that you may not even consider is getting a good night’s sleep. People with PD often experience sleep difficulties, including vivid dreams, sleeplessness, restless leg, and even daytime drowsiness. There are a number of things you can do to sleep well, such as avoid caffeine or other stimulants, avoid oversleeping, go to bed and get up at the same time each night and day, and even minimize how much fluid you drink at night before bedtime.
Finally, emotional well-being is important. Living with PD brings a range of emotions, and it’s a good idea to keep engaged with hobbies you love, friends, and even support groups. You can find support groups right here in the community or online.

33. Nutritional concerns in PD
Maintaining proper weight and calorie intake
Dealing with constipation
Supporting bone health
Managing protein and levodopa
Another aspect of treatment is nutrition. While eating healthy is important for everyone, people with Parkinson’s do have some specific nutritional concerns.
First, maintaining a proper weight is sometimes a challenge. PD tends to cause weight loss over time for a variety of reasons, including the fact that many patients lose their appetite as part of the disease.
Many people living with PD suffer from constipation, which is a symptom of the disease.
Keeping bones strong is also important because as a person with PD, your risk of falls is greater.
And finally, the effectiveness of levodopa may be affected by protein, so you’ll need to manage how much protein you eat.
Holden K. Parkinson's disease: nutrition matters. National Parkinson Foundation. Available at

34. PD resources National Parkinson Foundation www.parkinson.org
Parkinson’s Disease Foundation
American Parkinson’s Disease Association
Local Parkinson’s Support Group
My last slide is a list of some online resources that are good sources of information on Parkinson’s and available treatments.
In addition, I have copies of some literature you may be interested in after the presentation.
Thank you, and have a good evening.
AZL /101067

35. Questions?
Dr. Mariecken Fowler
Office phone:
(540)