1. PERSPECTIVES ON PARKINSON’S
Terry Watkins MSN,
CRNP
Second most common neurodegenerative disease in the CNS in the elderly next to Alzheimers
Mean set is 57 with 4% diagnosed before age 50.- How many might be missed?
Involves the malfunctioning and death of many neurons starting in the midbrain.
1 million people in the US have PD
Parkinsons is part of a subset of Parkinsonism
and referred to as idiopathic- the largest subgroup-78%.
Lets look at the face of parkinson disease:
Imagine your self not being able:
to write your name or sign a check book because of a tremor
not being able to turn in bed with out difficulty
drive a car because your foot gets stuck on the accelerator
cannot smell roses in the garden
you begin to see things that no one else sees- wolves attacking your cat
cannot button your clothes
you have this overwhelming desire to start hoarding garden tools in your house and your wife is not interested in doing anything about it
Seems like you can think of is having sex 24 hours a day
Wife is complaining and also exhausted.
Wake up in the middle of the night living through a dream that was so vivid you slugged you mate in the bed next to you.
These are the face of PD as we see the disease progress.
How many of you know someone that is has PD that is either a family member or an acquaintance?15-25% of people report a relative with PD
No different:It shows no ethnic, social, economic or geographic boundaries.

3. HISTORY
An Essay
on the
SHAKING PALSY By
James Parkinson
London
1817
1500- Leonardo De Vinci identified a “paralytic” condition involving a tremor in the limbs
1700- John Hunter, a British surgeon
described patients with a
severe tremor
First described in classic monograph “ An Essay on the Shaking Palsy.”
PD is a chronic, progressive movement disorder with loss of dopamine generating cells in the brain that results in a complex array of symptoms. e
Traditionally thought of as a motor system disorder, now recognized as a complex condition with diverse clinical features that include autonomic dysfunction, and neuropsychiatric symptoms.
1817- James Parkinson published the
Essay on the Shaking Palsy

4. Brain Image of the Substantia Nigra
pathology of this disease:horizontal cut of the brain:
PD is a brain disorder when dopamine is depleted in the brain. Dopamine allow for the coordinated smooth movement of the muscles. When 80% of these neuro transmitters are lost then the symptoms of PD appear is a depletion of the dopamanergic neuron in the substance nigra as well a atrophic changes. When 80 % of the dopamine producing cells are damaged, the motor symptoms become more evident.
Dopamine is a chemical messenger responsible for transmitting signals between the substantia nigra and the next "relay station" of the brain, the corpus striatum, to produce smooth, purposeful movement.The basal ganglia, located in the forebrain control movement. Acetylcholine is an excitatory neurotransmitter in the BG. Without dopa, inhibitory influences are lost and excitatory mechanism are unopposed leading to tremor and bradykinesia.

5. Clinical features emerge when 60-80% of the dopamine is lost

6. Inflammation/ infection and or Brain injury
Genes:
A vast majority are not directly inherited, but researchers have discovered several genes that can cause PD in a small number of families.
Inflammation/ infection and or Brain injury
Environment:
39% higher risk with exposure to herbicides
PD affects about 50 percent more men than women, and the reasons for this discrepancy are unclear.  While PD occurs in people throughout the world, a number of studies have found a higher incidence in developed countries.  Other studies have found an increased risk in people who live in rural areas with increased pesticide use.  However, those apparent risks are not fully characterized.
One clear risk factor for PD is age.  The average age of onset is 60 years, and the incidence rises significantly with advancing age.  However, about 5 to 10 percent of people with PD have "early-onset" disease that begins before the age of 50.   Some early-onset cases are linked to specific gene mutations such as parkin.  People with one or more close relatives who have PD have an increased risk of developing the disease themselves, but the total risk is still about 2 to 5 percent unless the family has a known gene mutation for the disease.  An estimated 15 to 25 percent of people with PD have a known relative with the disease injury:
28%- 1 knock out
156%- increased risk with 2 knockouts.
Environmental causes- Aberdeen study- found 39% higher risk with pt exposed to herbicides.
Moreover, increasing evidence suggests that early-life occurrence of inflammation in the brain, as a consequence of either brain injury or exposure to infectious agents, may play a role in the pathogenesis of PD. Most important, there may be a self-propelling cycle of inflammatory process involving brain immune cells (microglia and astrocytes) that drives the slow yet progressive neurodegenerative process.
Large pedigree of familial parkinsonism has been linked to a mutation of alpha synuclein.

7. T R A P- YOU GOT IT!! Signs of PD No Biomarker to diagnose the disease
Tremor-Not every tremor is PD
Rigidity- test with passive resistance of joint
Bradykinetic- “Slow movers”
Postural Instability- flexed knees and head
Autonomic symptoms seen early on: anosmia, RBD, constipation, RLS, akathisia
T R A P- YOU GOT IT!!
At a minimum, rigidity and a tremor must be present to consider the diagnosis of idiopathic PD. Trial of dopaminergic therapy is an important supportive feature of diagnosis.
Often See:
tremor - decreases with purposeful activities, unilateral, do not confuse with an essential tremor- often autosomal dominant, and intentional. Essent Tremor usually improves with alcohol.
2. Akinetic-Rigidity- increased resistance to pass movement, 90% occurrence. usually progresses to the other side, Cogwheeling-ratchety pattern of resistance.
4. Postural instabilty- “pull test”, pt is pulled by the shoulders from behind. normally-pt tried to regain balance by stepping back on step. With PD, he is likely to fall or take multiple steps
No biomarkers to pick up the disease or track it like PSA’s blood pressure. DAT scan can show the loss of dopamine and assist in the diagnosis.
Tremor - 70% of pts, starts off unilateral and then becomes bilateral
Brady kinetic- most disabling motor abnormality in PD. Difficulties performing daily functions, writing, feeding themselves, combing their hair and beating an egg, using the internet, zipping up clothes
Most cases of PD start between the ages of years of age. with peak at age 60.
Risk factors include: age, rural farming, infectious agents, exposure to MPTP compounds, pesticides and herbicides.
other factors that are assoc with decreased risk are cigarette smoking and caffeine intake
TREMOR, RIGIDITY, AKATHESIA, POSTURAL INSTABILITY
The four primary symptoms of PD are:
• Tremor. The tremor associated with PD has a characteristic appearance.  Typically, the tremor takes the form of a rhythmic back-and-forth motion at a rate of 4-6 beats per second.  It may involve the thumb and forefinger and appear as a "pill rolling" tremor.  Tremor often begins in a hand, although sometimes a foot or the jaw is affected first.  It is most obvious when the hand is at rest or when a person is under stress.  Tremor usually disappears during sleep or improves with intentional movement.  It is usually the first symptom that causes people to seek medical attention.
• Rigidity. Rigidity, or a resistance to movement, affects most people with PD.  The muscles remain constantly tense and contracted so that the person aches or feels stiff.  The rigidity becomes obvious when another person tries to move the individual's arm, which will move only in ratchet-like or short, jerky movements known as "cogwheel" rigidity.
• Bradykinesia.  This slowing down of spontaneous and automatic movement is particularly frustrating because it may make simple tasks difficult.  The person cannot rapidly perform routine movements.  Activities once performed quickly and easily—such as washing or dressing—may take much longer.  There is often a decrease in facial expressions.
• Postural instability.  Postural instability, or impaired balance, causes affected individuals to fall easily.
PD does not affect everyone the same way, and the rate of progression and the particular symptoms differ among individuals. 
PD symptoms typically begin on one side of the body.   However, the disease eventually affects both sides.   Even after the disease involves both sides of the body, the symptoms are often less severe on one side than on the other. 
Friends or family members may be the first to notice changes in someone with early PD.  They may see that the person's face lacks expression and animation (known as "masked face") or that the person moves more slowly.
Early symptoms of PD may be subtle and occur gradually.  Affected people may feel mild tremors or have difficulty getting out of a chair.  Activities may take longer to complete than in the past and individuals may note some stiffness in addition to slowness.  They may notice that they speak too softly or that their handwriting is slow and looks cramped or small.  This very early period may last a long time before the more classical and obvious motor (movement) symptoms appear.
As the disease progresses, the symptoms of Parkinson's disease may begin to interfere with daily activities.  Affected individuals may not be able to hold utensils steady or they may find that the shaking makes reading a newspaper difficult.  People with PD often develop a so-called parkinsonian gait that includes a tendency to lean forward, taking small quick steps as if hurrying (called festination), and reduced swinging in one or both arms.  They may have trouble initiating movement (start hesitation), and they may stop suddenly as they walk (freezin
What other diseases and conditions resemble Parkinson's disease?
A number of disorders can cause symptoms similar to those of PD.  People with symptoms that resemble PD but that result from other causes are considered to have parkinsonism. 

8. TREATMENT FOR PD- Old and New
Levadopa Carbadopa- “Gold standard” Rule is to “go slow.” Can do a trial run
Rytary- extended release
Duopa- Used in Advanced disease, Peg tube
Consider: Drug Induced Parkinson’s- a number of drugs interfere with dopaminergic transmission
THE DISEASE MOVES ON DESPITE TREATMENT
Levadopa/Carbidopa- minimize the effects of acute side effects if goes slow. - nausea and hypotension. Improves, tremor, rigidity and bradykinesia. although is one of the best PD medications, it has its share of side effects: anorexia, insomnia, motor fluctuations, dyskinesia, neuropsychiatric disorders.
Rytary
duopa_ treatment of motor symptoms, suspension form of levodopand carbadopa, continuous pump thru a pump into the intestine for up to 16 hrs.
Drugs that deplete Dopamine or block the receptors- akathisia is the most common manifestation. Get a good history of any new medications, ask about neuroleptics, regional. Are you masking idiopathic PD.
Exercise !!!! on of the BEST Therapies LSVT BIG and LSVT LOUD

9. How Medications Work in Parkinson's Disease
While there is currently no cure for PD, there is a wide range of treatments that effectively alleviate Parkinson’s symptoms. speaking, these treatments either replenish dopamine levels or mimic the action of dopamine in the brain
Levodopa-is broken down rapidly in the body, so carbadopa, decarboxylase inhibitor, is added to prevent the to block the conversion to dopamine in the systemic circulation and liver before it crosses the BBB.-causing its effect on symptom control to fade out or wear off.
Dopamine agonists actually mimics the effects of dopamine without having to be converted. Mirapex, requip- given early on for motor symptoms.
Dosing tips- start slow and titrate the lowest dose that produces the best clinical response - higher doses- dyskinesia and hallucinations and Compulsions.
While there is currently no cure for PD, there is a wide range of treatments that effectively alleviate Parkinson’s symptoms. These treatments offer people with PD an improved quality of life and give them more opportunity to carry out their daily activities.The discovery that PD is associated with low levels of dopamine, the chemical messenger in the brain, has paved the way for the development of current medicinal treatment strategies. Broadly speaking, these treatments either replenish dopamine levels or mimic the action of dopamine in the brain (Figure 2). Dopamine levels can be replenished with various medicines based on levodopa (L-dopa), a drug that is converted to dopamine in the brain. Dopamine levels can also be increased by medicines called monoamine oxidase B inhibitors which prevent dopamine from breaking down in the brain. Other medicines called dopamine agonists (e.g. sifrol) can mimic the action of dopamine (Figure 2).

10. DOPAMINE AGONISTS
Dopamine Agonists-stimulate dopamine receptors. Are direct agonist-
Monotherapy- useful in early disease
Adverse effects are similar to those of levodopa
Impulse Control Behaviors- prescribers should specifically ask pt and caregivers about the development of new or ICB while being treated
Do not require metabolic conversion and do not compete with amino acids for transport across the gut into the brain.
Monotherapy- levodopa can be postpone and saved for later time in the course of the disease when disability worsens. There can be a reduced response to levodopa and a decline in drug response. this medication has been helpful.
In 16 trials, comparing DA with levodopa, pt assigned to DA arm treatment were less likely to develop dyskinesia
Adverse effects: nausea, sleepiness, orthostatis hypotension, confusion and hallucinations- 15% experienced Hallucinations with DA in one study
Impulse Control behaviors refers to a group of behaviors that are compulsive in nature. In one study, 145 people with PD experience one of more of the ICB. Suspect that the prevalence might be higher. If he had experienced one ICB then there was a % chance of experiencing 2 or more.
Can be a associated with dopamine dysregulation and or hypersensitivity to overreact to the medication.
Study- two often most common drugs seen are Mirapex and equip. Can also be seen with other meds but not as frequent. If the dose is lowered less SE.

11. Hobbyism Gambling Excessive spending Examples of Behaviors punding
Examples of Impulse Control Behaviors
ICD
Examples of Behaviors
punding
purposeless repetitive behaviors, like rearranging objects
taking things apart or putting things together
Hobbyism
intensive or hyper focused time spent on specific hobbies
crafting and knitting of long hours
Excessive spending
large purchases
, excessive generosity, purchasing excessive amounts of the same thing
Eating disorders
binge eating and frequent hiding foods
Hpersexuality
Pathological hypersexuality,
inappropriate demands sexual demands
obsession with porn, lewd behaviors,
Gambling
excessive casino gambling
internet gambling, risky investments
Men more susceptible to hypersexuality and pathological gambling
Women are often seen- excessive eating and shopping

12. Wake Up, there is More to Come

14. Psychosis is a complication of PD that causes a significant morbidity, caregiver burden and frequently results in nursing home placement. What is important is to distinguish this psychosis with PD and other conditions. For example, LewyBody demenita psychosis presents early on in the disease whereas PS psychosis presents later on in the disease. PD starts in the back of the brain in the midbrain and moves forward. LBody starts in the front on the brain and move backward.
All these diseases are a clinical diagnosis so important to diagnose correctly.
Visual hallucinations are most commonly seen

15. National Institute of Neurologic Disease and Stroke Neurology Institute of Mental Health
Hallucinations- are either visual or auditory
Delusions- are false beliefs
Has to occur in pt that have already been diagnosed with Pd.

16. Disease Progress is a key Factor contributing to Pd Disease Psychoses
Intrinsic factors include: the disease itself starting in the cerebellum and moves forward in the brain, as the disease progresses see a lot of neurodegenerative changes with accumulation of alpha syneuclin proteins in the brain.
Extrenisic- medications cn contribute, especially in the D and also it is inherent in the disease. Hard to separate the two out.
Other environmental causes- later in the day, less exposure to sunlight, lack of stimuli and interactions with others

17. This slides speak to the intrinsic part of the puzzle of the disease
Early on in the disease hallucinations are beginning but has has not lost insight- sees dog and dog died but he know the dog died
laster on he see the dog and it is now a pack of wolves in the bathroom, does not recognize it for a hallucination but believes it to real.
Later on the the disease take it toll, alarms their caretakers and others. will respond aggressively and fight back, even hitting their caretakers, destroying property.
Cannot say that if this person is treated early would this prevent this from happening- long term studies will help with this.
When they become desruptive- then the decision is to treat them.
The data this time cannot say that the psychosis caused the mortality but long term studies will help to determine these questions.

19. The thing that makes Pimavanzserin unique is its specificity with ic described in this function binding chart here.
The smaller the umber the tight the binding. If you have tight binding you only need a small number of receptors to bind with that activity.

21. Unified Parkinson Disease Rating Scale
II- ADL
III- Motor function
Screened at 2,4,6 weeks

27. Tips for Advanced Practitioners
Exercise is Vital
Do not skip or postpone doses
Be alert to ICD and Psychosis
Refer to a Neurologist, if needed
Exercise has proven to build healthier hearts, muscles and lungs.
Research has shown with PD to be neuro
protective and slowing the progression
Resume medications immediately after any procedure, vomiting
or while in the hospital take it on time

28. Parkinson Association of Central Alabama
Montgomery Parkinson’s Support Group
Meets at Frazier United Meth. Church
4th Thursday of every month 6pm
National Parkinson Foundation
Michael J. Fox Foundation

30. Hang On What is ImportantTo
What is Important
This is Will my grandson that is 18 mon hanging on to the dishwasher.
Continue to support your adv. practitioner regional groups, become a member of the NPAA
Remember