Edith Cowan University: Clinical Update on Parkinson's Disease

This report presents a comprehensive clinical update on Parkinson's Disease, a progressive neurodegenerative disorder. It begins with an introduction to the disease, its prevalence, and the five identified stages. The report details the aetiology and pathophysiology, including the role of dopamine reduction, genetic mutations (LRRK2, GBA, SNCA), and environmental factors. It outlines the progression of the disease according to Braak’s hypothesis, touching upon non-motor symptoms like hyposmia and constipation. Diagnostic methods, including SPECT scans, MRI, CT scans, and pathological tests, are discussed alongside the use of the Optimised Cuttlefish Algorithm. The clinical manifestations, prognosis, and treatment procedures, including pharmacological interventions like Carbidopa-Levodopa, dopamine agonists, MAO-B inhibitors, and surgical procedures like deep brain stimulation, are thoroughly examined. The report also addresses public health implications, such as reducing pesticide use and promoting omega-3 fatty acid intake. The conclusion summarizes the key findings and emphasizes the importance of early intervention.

PARKINSON DISEASE

1
Assignment Title:
Unit code and Title:
Name of Tutor:
Name of Student:
Student Number:
Date of Submission:
Total Word Count:

2
Table of Contents
Introduction:...........................................................................................................................4
Aetiology and pathophysiology:............................................................................................4
About Parkinson disease....................................................................................................4
Pathophysiology:................................................................................................................5
Progression of the disease:.................................................................................................5
Incidence World of Parkinson’s disease:...............................................................................6
National diagnostic method:..................................................................................................6
Prognosis and Clinical manifestation of Parkinson disease:..................................................7
Clinical manifestations:......................................................................................................7
Prognosis:...........................................................................................................................7
Treatment procedures:............................................................................................................8
Public health implications:.....................................................................................................9
Conclusion:..........................................................................................................................10
References:...........................................................................................................................11

3
Introduction:
Parkinson disease is a prevalent neurodegenerative disease which mainly leads to loss
of muscle contraction (Poewe et al., 2017). This disease is primarily caused by the
breakdown of neuron in the brain leading to reduced dopamine levels and finally causing
Parkinson disease. It is found that over ten million people throughout the world are affected
by Parkinson disease until today (Tysnes & Storstein, 2017). Five stages have been identified
in Parkinson disease. These stages start from mild symptoms of the disease and end at the
most advanced stage of the disease, in which the person experiences hallucinations and
deliriums (Berg et al., 2015). At the end of this paper, interventions for public health
promotion and treatment strategies for the prevention of Parkinson disease is also discussed.
Aetiology and pathophysiology:
About Parkinson disease:
Parkinson disease is a progressive disorder of the nervous system. This disease is
caused by the breakdown of nerve cells in the brain, that produce chemical messengers. One
of these chemical messengers is dopamine. Reduction in dopamine concentration in the brain
causes brain dysfunctions (Burbulla et al., 2017). The researchers identified specific gene
mutations as the primary cause of Parkinson disease. These genes include lrrkk2, gba and
snca genes. Mutation in all of the above-stated genes leads to the destruction of neurons and
ultimately making the host vulnerable to the disease. A secondary cause of this disease was
found to be certain environmental factors such as the incorporation of toxins into the host's
body. Toxins directly cause mutations in the genetic organisation of the host, increasing the
chances of Parkinson disease.

4
Pathophysiology:
The pathophysiology of this disease starts with the stages of Parkinson disease.
Parkinson disease constitutes of five stages (Berg et al., 2015):
Stage 1: During the initial stages, the person experiences mild symptoms, including
tremor and other movement symptoms along on a particular side of the body only.
Stage 2: On this stage, the patient experiences rigidity along with the problems
associated with tremor. Rigidity is a condition in which the person's movement is obstructed
by his bones and muscles. The no longer function as voluntary.
Stage 3: The main symptoms of this stage are a loss of balance, posture problems and
gradual loss of movements. This stage is called the mid stage of the stages of Parkinson
disease. Independent nature of the person's activities are observed; however, impaired
activities in having food or during dressing is also observed.
Stage 4: This stage is the penultimate stage of this disease. Symptoms get much more
severe in their nature, where unassisted standing up of the patient is observed. However, the
person requires assistance during his or her movement. It has also been found that the person
could not live alone, being in this stage of the disesase.
Stage 5: This is the stage in which the patient is at the weakest state where legs
become very stiff, not allowing the person to stand up or walk. A wheel chair is mostly
required by the person to assist him or her in movement. Along with these symptoms, the
person experiences from hallucinations and deliriums also, which needs further treatments.
Progression of the disease:
According to Braak’s hypothesis (Rietdijk et al., 2017), the primary symptoms of
Parkinson’s disease are centred around enteric nervous systems, olfactory bulb and medulla.
All the above three parts are connected to smell receptors in the human body. It is also stated

5
that Parkinson disease progresses to substantia nigra and cortex after a long time of onset.
This theory states that non-motor factors such as hypsomia (loss of smell sense), disorders of
sleep and constipation are the most common symptoms of this disease across the world. As a
result, these non-motor factors have been used by the researchers to diagnose the diseased
condition.
Incidence World of Parkinson’s disease:
Occurrence of Parkinson disease is two people per one thousand people in a
population concerned at any time (Ascherio & Schwarzschild, 2016). The prevalence of this
disease has been increasing with the age of the population concerned. Only one per cent of
people above sixty years of age has been found to be affected by Parkinson disease. In 2016,
6.1 million people throughout the world were found to be affected by Parkinson disease as
compared to 2.5 million for the year 1990 (Dorsey et al., 2016). Therefore, it has been found
that the occurrence of this disease throughout the world is high; however, the prevalence is
very high in percentiles.
National diagnostic method:
It has been found that no specific tests exist for diagnosing Parkinson disease. SPECT
(Single-photon emission computerised tomography) scan, is the first diagnosis process to be
applied. This process is a technique to scan the dopamine transporters present in the neurons.
Imaging tests can also be performed such as MRI (Magnetic Resonance Imaging), CT scan
(Computerised Tomographic scan) and ultrasonography of the brain. These tests will provide
direct evidence of the lack of neurons in the brain (Bhat et al., 2018). Pathological tests such
as blood test can also be performed to diagnose the disease. A theory termed as Optimised
Cuttlefish Algorithm, is being used by health professionals to diagnose Parkinson disease
(Gupta et al., 2018 ). In this strategy, Parkinson speech and handwriting datasets are used to
diagnose the disease. It has been found that ninety-four per cent of the patients were correctly

6
diagnosed by this method (Gupta et al., 2018). These are the diagnosis strategies used by the
health professionals throughout the world to diagnose Parkinson disease.
Prognosis and Clinical manifestation of Parkinson disease:
Clinical manifestations:
Clinical manifestations of Parkinson disease involves different stages of the disease,
which was discussed in brief in previous sections. There is a different method of treatment
exists for the particular stages of the disease. Molecular structure of the disease course plays a
significant role in the clinical manifestation of Parkinson disease. Mitochondrial dysfunction
and oxidative stress are to major disorders, that control the Parkinson disease from the
molecular level. According to Liu, (2017), pink1 gene is changed in its configuration during
the disease manifestation. This change in host genetic configuration causes autosomal
recessive Parkinson disease. Mitochondria stop functioning correctly and thus, various
metabolic disorders have been found to occur. Host fails to produce enough energy in the
form of ATP, which will aid in the proper functioning of the muscle system in the body. The
stages of this disease are based on the level of destruction of the genes in the molecular level.
Missense and truncating mutations in the genetic level have been found to be responsible for
the change in the genetic organisation of the above-stated gene. Some other genes are also
affected by these mutations like lkkr1, snc, gap and a few others (Kalinderi, Bostantjopoulou
& Fidani, 2016).
Prognosis:
The first stage involves very mild movement problems associated with the patient.
This stage serves as a particular diagnostic stage for most of the Parkinson diseased patients.
Treatments mainly are not provided at this stage, before the disease is confirmed at later
stages. In the second stage, the patient experiences from tremor. Tremor is mainly associated
with involuntary and rhythmic contractions of muscles which can be cured by taking a few

7
drugs. Drugs include Beta blockers, mysoline and Topamax (Pagano et al., 2015).
Topiramate is one of the most useful drugs to treat tremor associated with Parkinson disease.
The third stage involves balance and posture loss associated with the patient. These physical
disorders can be primarily treated with physiotherapy; however, this technique will no longer
solve the disorder if the onset of Parkinson has begun. Anti-vertigo and anti-nausea
medications are provided to treat the balance and posture problem in patients. Stage four and
five are more advanced stages of Parkinson disease. These stages involve primary and
secondary medications to treat the condition. During these stages, the body is wholly affected
both externally and internally. Complications' occur when the patient fails to move from his
place and cannot express their feelings. Levodopa or L-Dopa has been used as the best drug
for treating patients at stage five of Parkinson disease (Bastide et al., 2015). This strategy
solves the stiffness in muscles and rigidity of the muscles by starting the neuron actions
again. Dopamine is increased in concentration in blood, which compensates the loss of
neurons during Parkinson disease.
Treatment procedures:
The treatment procedures mainly include curing the condition of tremor, walking and
movement problems. Substitutes of dopamine can also be used as a medication, which was
discussed in very brief in the above section.
Carbidopa-Levodopa: Levodopa is a natural chemical, which is found to cross the
brain barriers and enter the core of the brain. On reaching the brain, this chemical gets
converted to dopamine. Carbidopa is combined with levodopa. This technique prevents
levodopa from converting to dopamine, befor it reaches the brain (). Side effects are mainly
nausea and orthostatic hyportension. The efficiency of levodopa may wear off after years of
its application.

8
Antagonists of dopamine: Pramipexole, ropinirole, and rotigotine acts as antagonists
of dopamine, which substitute dopamine, in the transporters.
Inhibitors of MAO B: These drugs prevent the catabolism of dopamine in the brain
by causing an inhibition of the enzyme action, monoamine oxidase B (MAO B). This enzyme
metabolises dopamine. Insomnia and nausea can be observed as side effects.
Inhibitors of Catechol O-methyltransferase (COMT) inhibitors: The primary
medicine of this class is Entacapone or comtan. This medication lengthens the effect of
levodopa therapy. Tolcapone is another COMT inhibitor. Side effects mainly include liver
damage, diarrhoea and others.
Amantadine: Mild stages of Parkinson disease can be treated by taking amantadine.
This drug helps to control involuntary movements which occur due to levodopa therapy.
Other treatment plans include surgical procedures that include deep brain
stimulations. This procedure provides incorporation of electrodes into the brain of the
patient, by the surgeon. A generator is placed near the chest of the patient, and other ends of
electrodes are connected to it. DBS stabilises involuntary movements, reduces tremor,
rigidity and improves the movement processes of the patient. Side effects include the
occurrence of stroke, infection and brain haemorrhage. Although surgical procedures are
effective, but also, there are a lot of risk factors associated with them (Sousa et al., 2018).
Public health implications:
Reduction of the use of artificial insecticides and pesticides in the agricultural fields.
These, in turn, incorporates toxins in the brains of people via their blood circulation. Change
into organic sources of fertilisers can prevent the chance of occurrence of the disease.
Incorporation of omega-3-fatty acids in the diet can reduce the chances of presence of
Parkinson disease (Mori et al., 2018). This compound prevents the degeneration of cells and

9
neurons present in the human body. Coenzyme Q10 can also remove the chance of
occurrences of Parkinson disease (Negida et al., 2016). This compound functions as an anti-
oxidant and helps in the removal of reactive oxygen species in blood. Reactive oxygen
species are mainly generated by incorporation of toxins into the human body. Other public
health promotion factors can be providing education about Parkinson disease to the public.
This procedure can be achieved by launching education camps, providing leaflets to
pedestrians and also organising public seminars based on Parkinson disease risk factors and
prevention.
Conclusion:
On a concluding note, it can be stated that Parkinson disease is a neurodegenerative
disorder, which is associated with both physical and psychological problems in human being.
On its progression through five stages, this disease can permanently end a human life, if not
taken care of at an early stage. Although direct diagnosis techniques are not available,
imaging techniques can quickly provide evidence of the disease. Treatment of this disease by
using several medicinal drugs is possible regardless of the side effects of the medicines.
Lastly, if public health is adequately taken care of by proper awareness about the disease,
there can be good hope in the near future. Parkinson disease, although it has no direct
evidence of occurrence if caught at an early stage, this disease can be cured fully and finally
eliminated from the world.

10
References:
Ascherio, A., & Schwarzschild, M. A. (2016). The epidemiology of Parkinson's disease: risk
factors and prevention. The Lancet Neurology, 15(12), 1257-1272.
https://doi.org/10.1016/S1474-4422(16)30230-7
Bastide, M. F., Meissner, W. G., Picconi, B., Fasano, S., Fernagut, P. O., Feyder, M., ... &
Fisone, G. (2015). Pathophysiology of L-dopa-induced motor and non-motor
complications in Parkinson's disease. Progress in neurobiology, 132, 96-168.
10.1016/j.pneurobio.2015.07.002
Berg, D., Postuma, R. B., Adler, C. H., Bloem, B. R., Chan, P., Dubois, B., ... & Lang, A. E.
(2015). MDS research criteria for prodromal Parkinson's disease. Movement
Disorders, 30(12), 1600-1611. 10.1002/mds.26431.
Bhat, S., Acharya, U. R., Hagiwara, Y., Dadmehr, N., & Adeli, H. (2018). Parkinson's
disease: Cause factors, measurable indicators, and early diagnosis. Computers in
biology and medicine. 10.1016/j.compbiomed.2018.09.008
Burbulla, L. F., Song, P., Mazzulli, J. R., Zampese, E., Wong, Y. C., Jeon, S., ... & Savas, J.
N. (2017). Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in
Parkinson’s disease. Science, 357(6357), 1255-1261. 10.1126/science.aam9080
Dorsey, E. R., Elbaz, A., Nichols, E., Abd-Allah, F., Abdelalim, A., Adsuar, J. C., ... &
Dahodwala, N. (2018). Global, regional, and national burden of Parkinson's disease,
1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The
Lancet Neurology, 17(11), 939-953. https://doi.org/10.1016/S1474-4422(18)30295-3

11
Gupta, D., Julka, A., Jain, S., Aggarwal, T., Khanna, A., Arunkumar, N., & de Albuquerque,
V. H. C. (2018). Optimised cuttlefish algorithm for diagnosis of Parkinson's disease.
Cognitive systems research, 52, 36-48. https://doi.org/10.1016/j.cogsys.2018.06.006
Kalinderi, K., Bostantjopoulou, S., & Fidani, L. (2016). The genetic background of
Parkinson's disease: current progress and future prospects. Acta Neurologica
Scandinavica, 134(5), 314-326. https://doi.org/10.1111/ane.12563
Liu, Z., Zhou, T., Ziegler, A. C., Dimitrion, P., & Zuo, L. (2017). Oxidative stress in
neurodegenerative diseases: from molecular mechanisms to clinical applications.
Oxidative medicine and cellular longevity, 2017.
https://doi.org/10.1155/2017/2525967
Mori, M. A., Delattre, A. M., Carabelli, B., Pudell, C., Bortolanza, M., Staziaki, P. V., ... &
Ferraz, A. C. (2018). Neuroprotective effect of omega-3 polyunsaturated fatty acids in
the 6-OHDA model of Parkinson's disease is mediated by a reduction of inducible
nitric oxide synthase. Nutritional neuroscience, 21(5), 341-351.
https://doi.org/10.1080/1028415X.2017.1290928
Negida, A., Menshawy, A., El Ashal, G., Elfouly, Y., Hani, Y., Hegazy, Y., ... & Rashad, Y.
(2016). Coenzyme Q10 for patients with Parkinson's disease: a systematic review and
meta-analysis. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug
Targets-CNS & Neurological Disorders), 15(1), 45-53.
https://www.ingentaconnect.com/content/ben/cnsnddt/2016/00000015/00000001/
art00007
Pagano, G., Tan, E. E., Haider, J. M., Bautista, A., & Tagliati, M. (2015). Constipation is
reduced by beta-blockers and increased by dopaminergic medications in Parkinson's

12
disease. Parkinsonism & related disorders, 21(2), 120-125.
https://doi.org/10.1016/j.parkreldis.2014.11.015
Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., ... & Lang,
A. E. (2017). Parkinson disease. Nature reviews Disease primers, 3, 17013.
https://www.nature.com/articles/nrdp201713
Rietdijk, C. D., Perez-Pardo, P., Garssen, J., van Wezel, R. J., & Kraneveld, A. D. (2017).
Exploring Braak’s hypothesis of Parkinson’s disease. Frontiers in neurology, 8, 37.
https://doi.org/10.3389/fneur.2017.00037
Sousa, T. A., Ferret-Sena, V., Coelho, M., Correia-Guedes, L., Fabbri, M., Rosa, M. M., &
Godinho, C. (2018). Main reasons for rejection of deep brain stimulation surgery in
candidates with Parkinson Disease. Annals of Medicine, 50, S18-S19.
https://doi.org/10.1016/j.rpsp.2014.10.003
Tysnes, O. B., & Storstein, A. (2017). Epidemiology of Parkinson’s disease. Journal of
Neural Transmission, 124(8), 901-905.
https://link.springer.com/article/10.1007/s00702-017-1686-y