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SUMMARY

This report discusses the most common neurodegenerative disorder, Parkinsons disease,which affect about 1% of the population over age 60. Parkinsons disease (PD) is a

progressive neurological condition characterized by both motor (movement) and non-

motor symptoms. It is important to remember that presentation of symptoms is unique toeach person with Parkinsons. In this report, I will discuss what is Parkinsons disease,

what causes the PD, primary and secondary signs and symptoms, diagnostic methods,

treatments available and special considerations for PD patients and their family.

TABLE OF CONTENTS

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CONTENTS...................................................................................................................Page

ABRIVIATIONS ................................................................................................................ii

1 INTRODUCTION ............................................................................................................ 1

2 CAUSES of PARKINSON ..............................................................................................23 SIGNS and symptoms ..................................................................................................... 3

3.1 Primary Motor Symptoms .........................................................................................3

Resting Tremor ............................................................................................................... 3Bradykinesia ................................................................................................................... 3

Rigidity ........................................................................................................................... 4

Postural Instability .......................................................................................................... 4

3.2 Secondary Motor Symptoms .....................................................................................43.3 Non-motor Symptoms ...............................................................................................4

4 Diagnosis ...........................................................................................................................6

4.1 Pathology ................................................................................................................... 6

4.2 Clinical findings .........................................................................................................64.3 History ........................................................................................................................6

4.4 Imaging findings ........................................................................................................ 64.5 DNA testing options .................................................................................................. 7

5 Treatment .......................................................................................................................... 9

5.1 Drug Therapy ............................................................................................................. 9

5.2 Physical Therapy ........................................................................................................95.3 Stereotactic neurosurgery ...........................................................................................9

5.4 Fetal cell transplantation .......................................................................................... 10

6 Special considerations ....................................................................................................107 CONCLUSION ...............................................................................................................11

References .........................................................................................................................12

ABRIVIATIONS

PD Parkinsons disease

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PET Positron Emission Tomography

SPECT Single Photon Emission Computed Tomography

DNA Deoxyribonucleic acid

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1 INTRODUCTION

Parkinson's disease was named for James Parkinson, the English physician who wrote thefirst accurate description of the disease in 1817, Parkinsons disease characteristically

produces progressive muscle rigidity, akinesia, involuntary tremor, and dementia. Deathmay result from aspiration pneumonia or an infection.

Parkinson's disease is a neurodegenerative disease, in which there is death of neurons that

produce the neuronal signaling molecule dopamine. Parkinson's disease is the second

most common neurodegenerative disease. The depletion of dopamine causes a person to

have motor skill problems, such as resting tremors, slowness of movement, rigidity,flexed posture, and "freezing." These symptoms can be temporarily treated by the

administration of drugs that can replace dopamine. However, as the disease progresses

the treatments often stop working, and other symptoms such as depression, lack ofmotivation, passivity, and even dementia may develop. The cause of this disease is

unknown, despite much research of the subject.

Since Parkinson's often develops sporadically in older people, one hypothesis of its cause

involves the accumulation of oxidative damage to mitochondria, the energy producingorganelles of the cell, which then causes death of the cell. Murray et. al. (2003) have

recently shown that peroxynitrite (ONOO-), a dangerous oxidant which can form

spontaneously in mitochondria, can cause damage to and inhibit electron transportproteins that are involved in aerobic respiration and thus cellular energy generation. They

also used mass spectrometry and two-dimensional gel electrophoresis to identify sites of

oxidative damage of complex I, the damage of which is a feature of Parkinson's disease.These specific sites can now be used as markers of oxidative damage, and to determine

the role oxidative damage may have in neurodegenerative diseases.

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2 CAUSES OF PARKINSON

Although the cause of Parkinsons disease is unknown, study of the extra pyramidal brain

nuclei (corpus striatum, globus pallidus, and substantia nigra) has established that adopamine deficiency prevents affected brain cells from performing their normal

inhibitory function within the central nervous system.

The brain is particularly sensitive to death of cells, because neurons cannot regenerate,

and they constantly require a large amount of energy. A slow decrease in the number ofdopaminergic neurons occurs in all people throughout life (Nestler et. al, 2001, p. 313).

For most people, this decrease is not large enough to have visible effects (more than 60%

of these neurons must die for symptoms to develop), but 1-2% of people over 80 years

old develop Parkinsons disease (Ottley et. al, 1999). Many reasons have been cited forthe increased death of these cells in some people, including genetic factors, viral

epidemics and environmental toxins. Genetic factors are often found in people that

develop Parkinsons at an early age. Two gene defects have been linked to occurrence of

the disease: the genes alpha-synuclein and parkin. Alpha-synuclein and other proteinsform plaques called Lewy bodies that are found in the cytoplasm of the remaining

dopaminergic neurons in Parkinsons patients. This is thought to be caused by a defect inthe degradation of alpha-synuclein. Parkin is a newly discovered gene that is homologous

to alpha-synuclein (Nestler et. al, 2001, p. 313). Other genetic factors may include

mitochondrial DNA defects, which disrupt energy production and are maternallytransmitted. (Rosner, 1997) Usually, however, Parkinsons disease occurs sporadically

and not in families. Mitochondrial damage may also accumulate throughout a persons

life, and cause an energy deficiency that leads to the death of a neuron. In terms of

environmental factors, statistical analyses have linked rural living and exposure topesticides, certain viral epidemics, and exposure to heavy metals, especially Mn2+ and

Al-, to incidence of Parkinsons disease (Nestler et. al, 2001, p. 313-314). Incidenceincreases in persons with repeated brain injury, including professional athletes, andpersons using psychoactive substances, whether prescribed or illicit.

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3 SIGNS AND SYMPTOMS

The diagnosis of PD depends upon the presence of one or more of the four most common

motor symptoms of the disease, which are: resting tremor, bradykinesia, rigidity and

postural instability.

In addition, there are other secondary and non-motor symptoms that affect many people

and are increasingly recognized by doctors as important to treating Parkinsons.

Each person with Parkinson's will experience these symptoms differently. For example,

many people experience tremor as their primary symptom, while others may not havetremors, but may have problems with balance. Also, for some people the disease

progresses quickly, and in others it does not.

Symptoms of Parkinsons disease can widely be categorized as follows

Primary Motor Symptoms

Secondary Motor Symptoms

Non-motor Symptoms

3.1 Primary Motor Symptoms

Resting Tremor

About 70 percent of people with Parkinsons experience a slight tremor in the early stage

of the disease - either in the hand or foot on one side of the body, or less commonly in the

jaw or face. The tremor appears as a "beating" or oscillating movement. Because theParkinson's tremor usually appears when a person's muscles are relaxed, it is called

"resting tremor." This means that the affected body part trembles when it is not doing

work, and it usually subsides when a person begins an action. The tremor often spreads to

the other side of the body as the disease progresses, but remains most apparent on the

original side of occurrence.

Bradykinesia

Bradykinesia is the phenomenon of a person experiencing slow movements. In addition

to slow movements, a person with bradykinesia will probably also have incomplete

movement, difficulty initiating movements and sudden stopping of ongoing movement.

People who have bradykinesia may walk with short, shuffling steps (this is called

festination). Bradykinesia and rigidity can occur in the facial muscles, reducing a person's

range of facial expressions and resulting in a "mask-like" appearance.

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Rigidity

Rigidity, also called increased muscle tone, means stiffness or inflexibility of the

muscles. Muscles normally stretch when they move, and then relax when they are at rest.

In rigidity, the muscle tone of an affected limb is always stiff and does not relax,

sometimes resulting in a decreased range of motion. For example, a person who hasrigidity may not be able to swing his or her arms when walking because the muscles are

too tight. Rigidity can cause pain and cramping.

Postural Instability

People with Parkinson's disease often experience instability when standing or

impaired balance and coordination. These symptoms, combined with other symptoms

such as bradykinesia, increase the chance of falling. People with balance problems may

have difficulty making turns or abrupt movements. They may go through periods of

"freezing," which is when a person feels stuck to the ground and finds it difficult to start

walking. The slowness and incompleteness of movement can also affect speaking and

swallowing.

3.2 Secondary Motor Symptoms

The secondary motor symptoms include those below, but not all people with Parkinsonswill experience all of these.

Stooped posture, a tendency to lean forward

Dystonia

Fatigue Impaired fine motor dexterity and motor coordination

Impaired gross motor coordination

Poverty of movement (decreased arm swing)

Akathisia

Speech problems, such as softness of voice or slurred speech caused by lack of

muscle control

Loss of facial expression, or "masking"

Micrographia (small, cramped handwriting)

Difficulty swallowing

Sexual dysfunction

Drooling

3.3 Non-motor Symptoms

Non-motor symptoms of Parkinsons, such as sleep problems and depression, can be, formany people, as troublesome as the primary movement symptoms of the disease. The

following is a list of non-motor symptoms of Parkinson's disease.

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Pain

Dementia or confusion

Sleep disturbances

Constipation

Skin problems

Depression Fear or anxiety

Memory difficulties and slowed thinking

Urinary problems

Fatigue and aching

Loss of energy

Compulsive behavior

Cramping

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4 DIAGNOSIS

Precise diagnostic criteria for Parkinsons disease remain elusive. It is important todistinguish idiopathic Parkinsons disease from the broader term Parkinsonism.

Numerous neurodegenerative diseases may include a Parkinsons-like clinical picture,

including progressive supranuclear palsy and corticobasal degeneration. Parkinsonismcan also be a secondary feature of stroke or exposure to toxins such as the recreationaldrug ecstasy.

4.1 Pathology

Loss of pigmented neurons in the substantia nigra is a hallmark of Parkinsons disease.The presence of Lewy bodies is an important finding. However, Lewy bodies may be

seen in other neurodegenerative diseases, such as Alzheimer disease and multiple systems

atrophy. Some forms of Parkinsons disease, such as Parkin-related disease, may lack

characteristic Lewy bodies.

4.2 Clinical findingsThe classic features of Parkinsons disease include bradykinesia, tremor, rigidity and

postural instability.

4.3 HistoryMany patients will report other symptoms including: small handwriting, vivid dreams,

difficulty repositioning in bed, depression, anxiety, .etc.

4.4Imaging findingsPET and SPECT scanning can support, but not confirm, a diagnosis of PD, and are

considered experimental.

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.

A decrease in the neurotransmitter dopamine is seen on positron emission tomography(PET) of the brain as the disease progresses. (Red indicates high levels of dopamine,

blue low levels of dopamine.) Ottley et. al, 1999.

Figure 1: Progression of Parkinson's as seen on PET

4.5DNA testing options

Studies have identified numerous loci associated with a strong risk for developing PD.

These loci are

PARK1-Alpha synuclein (autosomal dominant parkinsonism)

PARK2-Parkin (autosomal recessive early onset, possibly dominant in some

families, may also be a modifying gene)

PARK3-unknown

PARK5-UCHL1 (susceptibility gene)

PARK6-PINK1 (autosomal recessive early-onset parkinsonism)

PARK7-DJ-1 (autosomal recessive early-onset parkinsonism)

PARK8-uknown (autosomal dominant parkinsonism)

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In addition to these major loci, numerous candidate gene studies have suggested

involvement of other loci in Parkinsons risk. These include polymorphisms in

detoxification genes such as glutathione s-transferase and cytochrome p450 genes. Othershave suggested a small increase in risk associated with the H1 haplotype of the taugene.

It is not yet clear how testing for such haplotypes/polymorphisms could be used clinically

to predict risk for PD. Such testing is not clinically available. As of the present time, theonly clinically available genetic testing for Parkinsons disease is sequencing and dosage

analysis of the Parkin gene (PARK2). While Parkin mutations are most frequent in

autosomal recessive juvenile Parkinsons disease, mutations have been described inisolated early onset cases, later onset recessive cases, and even some apparently dominant

pedigrees. Evaluation of the Parkin gene should include both sequencing and a

quantitative analysis to look for genomic rearrangements. A significant percentage of

Parkin mutations are large deletions that will not be detected by sequence analysis.Generally, laboratory data are of little value in identifying Parkinsons disease;

consequently, diagnosis is based on the patients age, history, and characteristic clinical

picture. Conclusive diagnosis is possible only after ruling out other causes of tremor,

evolutional depression, cerebral arteriosclerosis and, in patients younger than age 30,intracranial tumors, Wilsons disease, or phenothiazine or other drug toxicity.

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5 TREATMENT

Because Parkinsons disease has no cure, the primary aim of treatment is to relievesymptoms and keep the patient functional as long as possible. Treatment consists of

drugs therapy, physical therapy and, in severe disease states unresponsive to drugs,

stereotactic neurosurgery or the controversial treatment called fetal celltransplantation.

5.1 Drug TherapyPharmacological-dopaminergic agents, such as levodopa, improve symptoms in

Parkinsons disease. Its given in increasing doses until symptoms are relieved or adverseeffects appear. Because adverse effects can be serious, levodopa is frequently given in

combination with carbidopa to halt peripheral dopamine synthesis. Occasionally,

levodopa proves ineffective, producing dangerous adverse effects that include postural

hypotension, hallucinations, and increased libido leading to inappropriate sexual

behavior. In that case, alternative drug therapy includes anticholinergics such astrihexyphenidyl, antihistamines such as diphenhydramine, and amantadine, an antiviral

agent. There can also be significant fluctuations in the efficacy of the medicine. Someforms of Parkinsonism, such as progressive supranuclear palsy, may not respond well to

these agents.

Research on the oxidative stress theory has caused a controversy in drug therapy for

Parkinsons disease. Traditionally, levodopa-carbidopa has been a first-line drug in

management. However, it has also been associated with an acceleration of diseaseprocess. Inclusion of entacapone potentiates the effects of levodopa-carbidopa treatment

so that less frequent doses are required. Selegiline, an enzyme-inhibiting agent, allows

conservation of dopamine and enhances the therapeutic effect of levodopa. Selegiline

used with tocopherols delays the time when the patient with Parkinsons disease becomesdisabled.

5.2 Physical Therapy

Individually planned physical therapy complements drug treatment and neurosurgery tomaintain normal muscle tone and function. Appropriate physical therapy includes both

active and passive range-of-motion exercises, routine daily activities, walking, and baths

and massage to help relax muscles.

5.3 Stereotactic neurosurgery

When drug therapy fails, stereotactic neurosurgery, such as subthalamotomy andpallidotomy, may be an alternative. In these procedures, electrical coagulation, freezing,

radioactivity, or ultrasound destroys the ventrolateral nucleus of the thalamus to preventinvoluntary movement. This is most effective in young, otherwise healthy people with

unilateral tremor or muscle rigidity. Neurosurgery can only relieve symptoms. Surgical

treatments include surgical destruction of portions of the globus pallidus or thalamus.

This may improve some motor symptoms, but there is a significant risk of side effects.

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Deep brain stimulation, where by an electrode provide continual stimulation of globus

pallidus, subthalamic nucleus, or thalamus, may improve motor symptoms and/or tremor.

5.4 Fetal cell transplantationFetal stem cell transplantation, where fetal brain tissue is injected into the patients brain,

is still considered research, and mixed results have been seen. If the injected cells growwithin the recipients brain, they will allow the brain to process dopamine, thereby either

halting or reversing disease progression. Neurotransplantation techniques, including theuse of nerve cells from other parts of the patients body, have been attempted with

varying results.

Brain stimulator implantation alters the activity of the area where Parkinsons disease

symptoms originate. A pacemaker is implanted into the chest wall, and the electrode is

threaded (using magnetic resonance imaging for guidance) to the thalamus, pallidum, orsubthalamic nucleus. A successful procedure reduces the need for medication, thus

reducing the medication-related adverse effects experienced by the patient.

6 SPECIAL CONSIDERATIONS

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Effectively caring for the patient with Parkinsons disease requires careful

monitoring of drug treatment, emphasis on teaching self-reliance, and generouspsychological support.

Monitor drug treatment and adjust dosage, if necessary, to minimize adverse

effects.

Elderly patients may need smaller doses of antiparkinsonian drugs because of

reduced tolerance

If the patient has surgery, watch for signs of hemorrhage and increased

intracranial pressure by frequently checking level of consciousness and vitalsigns.

Encourage independence. The patient with excessive tremor may achieve partialcontrol of his body by sitting on a chair and using its arms to steady himself.

Advise the patient to change position slowly and dangle his legs before gettingout of bed. Remember that fatigue may cause him to depend more on others.

Help the patient overcome problems related to eating and elimination. For

example, if he has difficulty eating, offer supplementary or small, frequent meals

to increase caloric intake. Help establish a regular bowel routine by encouraginghim to drink at least 2 qt (2 L) of liquids daily and eat high-fiber foods. He may

need an elevated toilet seat to assist him from a standing to a sitting position.

Give the patient and his family emotional support. Teach them about the disease,

its progressive stages, and drug adverse effects. Show the family how to prevent

pressure ulcers and contractures by proper positioning. Inform them of the dietaryrestrictions levodopa imposes, and explain household safety measures to prevent

accidents. Help the patient and his family express their feelings and frustrations

about the progressively debilitating effects of the disease. Establish long- andshort-term treatment goals, and be aware of the patients need for intellectual

stimulation and diversion.

7 CONCLUSION

Parkinsons disease results from the death of brain cells that produce a substance called

dopamine, which the body needs for normal movement. By the time symptoms of

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Parkinsons disease become apparent, up to 80 percent of dopamine-producing cells have

been damaged. Parkinson disease is the most common neurodegenerative movement

disorder, which affect about 1% of population over age 60. There is no cure for PD whileonly symptom relief treatment exists. Also there is no such very obvious diagnosis

method to identify PD. However, PD does not cause death suddenly, while paralyzing the

patient very slowly with time, sometimes even after 15-20 years. At initial stage, PDsymptoms can be avoided by drugs. After some years, PD starts to not respond to drugs

and need to go for serious treatments like neurosurgery and fetal cell transplantation. PD

patient can do their day to day activities for long time with help of treatments and theyshould be encouraged while giving emotional support by family members for them to live

normal life.

REFERENCES

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Howstuffworks. (2009).How Parkinson's Disease Works. Retrieved 20th March 2009

from < http://health.howstuffworks.com>

Murray J, Taylor SW, Zhang B, Ghosh SS, Capaldi RA.(2003). "Oxidative damage to

mitochondrial complex I due to peroxynitrite: identification of reactive tyrosines by mass

spectrometry." J. Biol. Chem. 278(39):37223-30.

Nestler E, Hyman S, Malenka R. (2001). Molecular Neuropharmacology. 1st ed.

McGraw-Hill Companies. Inc.

Ottley R, Agbontaen J, Fodstad H. (1999). "Tailoring treatment for the Parkinson's

disease patient."JAAPA. March 01, 1999

Parkinson's Disease Foundation, Inc. (2009). Understanding Parkinsons. Retrieved 20th

March 2009 from http://www.pdf.org

Parkinsons Disease Society. (2009). Referred on 20th March 2009 from

Springhouse (2005).Professional Guide to Diseases (Eighth Edition)

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