Introduction. to researchers, men are more likely to

Introduction.

In 1817, James Parkinson’s described Parkinson’s disease as
a ‘shaking palsy’. Parkinson’s disease is a very complex disease and is termed
as a progressive neurodegenerative disease. The term fits appropriate as a
degeneration of the cells in the basal ganglia (substania nigra) takes place
and gradually worsens as time progresses. Within the UK, 1 in 500 people are
diagnosed with the disease and although Parkinson’s may affect people of all
ages and genders, the mean onset for the development of the disease is 55 years
old. Additionally, for reasons yet unknown to researchers, men are more likely
to develop the disease than women. Individuals diagnosed with Parkinson’s are
unable to produce the inhibitory neurotransmitter dopamine which is responsible
for motor control. However the reasons for the death and loss of the
dopaminergic cells remain unknown to researchers therefore meaning that the ultimate
pathogenesis of Parkinson’s remains unknown. Due to dopamine being an
inhibitory neurotransmitter, the loss of it causes an imbalance between
excitation and inhibition therefore leading to the symptoms of Parkinson’s
(tremor, bradykinesia, rigidity).

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Main body

The basal ganglia located in the brain deep beneath the
cerebral cortex is a group of nucleic and ‘anatomically are involved in the
processing of motor, limbic , sensory and associative information’    (J Reynolds, L Brownlie ,2015) .These
structures include the lentiform nucleus, caudate nucleus, subthalamic nucleus
and substania nigra.

 

The putamen and globus pallidus collectively make up the
lentiform nucleus in the basal ganglia.  The caudate nucleus plays a significant role
in the learning of the brain specifically in the storing and processing of
memories. Its work as a feedback processor means ‘it uses
information from past experiences to influence future actions and decisions’
(healthline medical team 2015). This means that it most valuable function comes
with the development of communication skills. 
In the basal ganglia, the subthalamic nucleus represents the sole
excitatory structure and plays the crucial role of the processing that is
carried out by the basal ganglia. In terms of Parkinson’s disease, the section
of the basal ganglia that is in heavy focus is the substania nigra. Initially recognised by Vicq d’Azir in 1786, ‘as a large cell mass located dorsal
to the cerebral peduncle at the basis of the mesencephalon’. Located in the midbrain, it is the region responsible
for the vital role of reward and movement. Often mistaken for one structure, it
is made up of two anatomically and functionally distinct parts the substania
nigra pars compacta and substania nigra pars reticulata. Its name is a
reflection of its dark appearance as substania nigra means ‘black substance’ in
Latin.

Located in the substania nigra is
the dopaminergic neurones. These neurones are responsible for the secretion of
the neurotransmitter dopamine. The pathophysiology of Parkinson’s is critically
dependant on these dopaminergic neurones. When a destruction of these dopaminergic
neurone occurs in a healthy human being, consequently there becomes a depletion
of dopamine stores therefore causing a degeneration of the dopaminergic
nigrostriatal pathway. Furthermore, in the corpus striatum, an imbalance of
excitatory (acetylcholine) and inhibitory (dopamine) neurotransmitters
occurs.  The deficiency of dopamine
(neurotransmitter involved in motor function) therefore leads to the complex
symptoms of Parkinsonism ‘compromising slowness of movement, difficulty in
initiating and ending movement, tremor and rigidity (S Mera, 1996).  There are clear differences in the dopamine
stores in those of healthy individuals in comparison to those who have
developed Parkinson’s disease as demonstrated by figure2.

 

Parkinson’s disease contains very distinctive symptoms and
its most noticeable feature is in the form of an uncontrollable resting tremor
which is usually presented in the arm and hand of the patient. The tremor
resembles a rotary action and therefore often referred to as ‘pin
rolling’.  The tremor is present whilst
the patient is at rest and increases in rhythmic movement and harder to control
when the patient is in an emotional or a stressed state. The tremor often
diminishes whilst in movement and in sleep. Although not all patients develop a
resting tremor, it is the most common and prevalent symptom of Parkinson’s as
70% of all patients diagnosed with the disease do eventually develop a resting
tremor.  Bradykinesia (a slowing of
movement) describes the slowness of conscious movement due to the increase in
difficulty for the patient to initiate or terminate a particular movement for
example getting out of chairs or walking. An extensive deal of concentration is
required for the patient to start and stop movement such as walking therefore
when in motion it occurs in a shuffling movement with very small steps. This
later leads to frustration as the patient is ‘aware of what to do but is
physically unable to do it’ (S, Mera, 1996). This can consequently lead to
akinesia – the disability for an individual to initiate movement.

Another common symptom of Parkinson’s disease is ‘cogwheel’
rigidity. This is muscle stiffness that can occur in any part of the body
causing stiffness and pain therefore limiting movement.  It is usually caused by an increase in muscle
tone due to the muscles being in constant state of slight contraction. As the
symptom develops in later stages, it may begin to affect to tongue therefore
leading to drooling. There are secondary list of symptoms that may also occur
as a result of Parkinson’s disease such as depression. According to the mental
health foundation, ‘Depression is different from feeling down or sad.
Unhappiness is something which everyone feels at one time or another, usually
due to a particular cause. A person experiencing depression will experience
intense emotions of anxiety, hopelessness, negativity and helplessness’. This
is common with individuals with Parkinson’s disease due to frustration obtained
from the inability to perform physical movements as well as chemical imbalances
in the brain as the depletion of dopamine is also heavily linked to the
development of depression.  Another
secondary symptom of Parkinson’s disease is constipation.   ‘Constipation
is a common condition that affects people of all ages. It can mean that you’re
not passing stools regularly or you’re unable to completely empty your bowel’
(NHS choices 2015).  Due to poor
peristalsis, sluggish bowel moment and the anticholinergic drugs used in
treatment of Parkinson’s patients do often suffer from constipation as a side effect.
Speech and memory difficulties are also evident in most patients suffering from
Parkinson’s.

Although the aetiology of Parkinson disease remains unknown,
researchers have outlined possible environmental and genetics links that
potentially lead to an increased chance of an individual to develop the
disease. For example studies show that people living in an industrial area or
working in industrial areas such as welders are more likely to develop
Parkinson’s due to exposure to heavy metals such as manganese lead, copper etc.
As mentioned previously, the disease is more common with individuals above the
ages of 60 and more common in males rather than females (reason unknown). Genetically,
Parkinson’s disease phenotype has been found on the long arm of chromosome 4
and although most cases of Parkinson’s are sporadic, in 10-15% of cases there
is a family hereditary history of the disease henceforth promoting a genetic
component to the disease however this may also just simply mean that some
family members are exposed to the same environmental agents.

 

 

There is currently no cure available for Parkinson’s
disease however there are various treatments available that can help improve
the quality of life on an individual living with Parkinson’s.  The most popular and common treatment for the
symptoms of Parkinson’s is in form of the drug levodopa (L-dopa). The idea is
to replenish the depleted dopamine stores inside the brain however dopamine
itself cannot cross the blood brain barrier due to in being too polar therefore
L-dopa a precursor of dopamine is used. L-dopa is able to successfully cross
the blood brain barrier and can then be converted into dopamine inside the
brain. However  the prescription of
decarboxylase inhibitor is required alongside L-dopa with the significant
reason of inhibiting the conversion of L-dopa into dopamine in the liver
maximising the amount of drug available for activity inside the brain where the
dopamine would be extremely beneficial toward the symptoms of Parkinson’s. The prescription
of decarboxylase also lowers the dosage of L-dopa required to generate
effectiveness.

 

Although the use of L-dopa is initially extremely
beneficial, it does carry its specific side effects such as wearing off due to
long term use making it almost effective less over a long period of time. It
can also potentially lead to movement disorders such as dyskinesia and
dystonia.  It can also be responsible for
side effects such as aggression and altered sleep. Another disadvantage of
L-dopa is although it does increase the life expectancy and alleviates
symptoms, it does not prevent the continued degeneration of the neurones
henceforth only produces symptomatic relief. Another drug that can be used for
the symptoms of Parkinson’s disease is amantadine and although it is less potent
than L-dopa, it has lesser side effects. It is thought to be involved in the
stimulation of dopamine from its granular stores though its precise mechanism
is unclear.  Monoamine oxidase B
inhibitors (MAO-B inhibitor) can also be prescribed for example selegiline can
extend the duration of symptom improvement if given in conjunction with L-dopa.
More specifically selegiline acts as a neuroprotective agents and therefore
slows down the progression of the disease. 

 

 

 

 

A different approach to drug treatment is the use of cell
transplantation. Cell Transplantation is the surgical process of replacing the
dopaminergic neurones lost in Parkinson’s disease which began in the late 1980’s.
 It is still in in experimental phase due
to encountering postoperative complications such as high mortality rates.  The process works by using grafted foetal
cells and according to neuroscience studies, “the adrenal medulla produces
dopamine normally and auto transplantation ensures that there will be no
rejection problems”. Post mortem studies of the individuals who have died show
that only a few of the grafted foetal cells survive. The process has also been
hit with many ethical issues where many people thought and felt that foetal
rights were being violated and that the use of foetal cells may encourage
abortions.    Many people also depend on
the use of therapies to help deal with the symptoms such as taking part in
regular exercise and taking advantage of physiotherapy can improve symptoms
such as bradykinesia.  The benefits of exercise
can also help with a lot of the secondary Parkinsonism symptoms such as
depressions as it can be a form of stress relief deviating patients from
depression.   

Conclusion

Although idiopathic Parkinson’s does not have a preventive
method nor a cure, there are medical improvements that have had positive
impacts towards living with the disease. Treatment such as gene therapy which focuses
on preventing the progressive degeneration of the neurones and also the
replenishing of the dopaminergic neurones. In my opinion I believe with the
power of science and dedication of doctors, the future of Parkinson’s is
getting much closer to a method much suitable for the cure rather than the
prevention and even although the romans have stated ‘prevention is better than
the cure’ I believe it will be much harder to prevent the degeneration of the neurones
leading to Parkinson’s than curing and replacing the neurones via different scientific
procedures. Furthermore, I believe the most important thing today is to focus
on the ways on maximising the quality of life for an individual with Parkinson’s
and helping them manage the disease as best as they possibly can.