Parkinson's disease is a neurodegenerative disease of the substantia
nigra (an area in the basal ganglia). The disease was first discovered
and its symptoms documented in 1817 (Essay on the Shaking Palsy) by the
British physician Dr. James Parkinson; the associated biochemical
changes in the brain of patients were identified in the 1960s.
The disease is a progressive movement disorder of the extrapyramidal
system, which controls and adjusts communication between neurons in the
brain and muscles in the human body.
The cause of Parkinson's disease is not known. Geneticists have since
1997 found nine different specific genetic defects, each of which causes
the disease in one or a few families with extraordinarily high
incidences of the disease, but such families are rare. While a strong
inheritance pattern occurs in only a very small percentage of cases, an
affected individual is three to four times more likely than an
unaffected individual to have a close relative with Parkinson's. Having
a parent with Parkinson's raises one's lifetime risk of developing the
disorder threefold, from the general population's figure of 2% to about
6%. Three of the genes that have been identified are alpha-synuclein,
Ubiquitin Carboxy terminal Hydrolosae L1 (UCH-L1) and Parkin.
A popular theory holds that the disease might result in most cases
from the combination of a subtle genetically determined vulnerability to
environmental toxins along with mild exposure to those toxins. The
toxins most strongly suspected at present are certain pesticides and
industrial metals. MPTP is used as the model for Parkinsons as it can
induce the disease in 20 year olds.
Minor past episodes of head trauma are also more commonly reported by
sufferers than by others in the population. While emotional or a
psychological trauma can precipitate the initial symptoms or aggravate
existing symptoms, this is not the actual cause of the disorder.
The symptoms of Parkinson's disease results in the loss of dopamine
secreting cells in the pars compacta region of the substantia nigra.
Which prevents the inhibition of the striatum, which causes increased
inhibition of globus pallidus external (GPe). This inturn results in
activation of the sub thalamic nucleus (STN), which excites the globus
pallidus internal (GPi) and pars reticula of the Substantia Nigra. Both
of which inhibit the thalamus. Ultimately resulting in reduced activity
in the motor cortex.
Brain cells producing other brain chemicals such as GABA,
norepinephrine, serotonin and acetylcholine exhibit minor damage in
Parkinson's disease, accounting for some of the wide array of symptoms.
The mechanism by which the brain cells in Parkinson's are lost
appears to center on an abnormal accumulation of the protein alpha-synuclein
in the damaged cells. This protein forms blobs called Lewy bodies. The
precise mechanism whereby aggregates of alpha-synuclein damage the cells
is not known. The aggregates may be merely a normal reaction by the
cells as part of their effort to correct a different, as-yet unknown,
insult. It does appear that alpha-synuclein aggregation is enhanced by
the presence of dopamine and the byproducts of dopamine production.
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- Decrease dopamine in putamen and substantia nigra
- Decrease noradrenaline and serotinine in the putamen
- Decreased synthesis of GABA
- Normal acetylcholine
This results in an overall excitatory outflow from the thalamus to the
If treatment with dopamine is excessive then there will be an overall
inhibitory outflow leading to the hyperkinetic syndromes.
Parkinson's disease is very widespread, with about 150-200 cases per
100,000 population at any given time. About 2% of the population
develops the disease some time during life. Cases are reported at all
ages, though it is quite rare in people younger than 30 and the average
age at which symptoms begin is 58-60; the risk of developing it
substantially increases with age. It occurs in all parts of the world,
but appears to be more common in people of European ancestry than in
those of African ancestry. Those of East Asian ancestry have an
intermediate risk. It is more common in rural than urban areas and men
are affected slightly more often than women.
Disease occurs at the age of 40 mainly in males.
Resting tremor: regular, rhythmic, exacerbated by emotional stress
and fatigue and disappear by sleep and voluntary activity (while this
is the best known symptom, it is not displayed by an estimated 30% of
Bradykinesia: slow automatic movements (arm swinging, monotonous speech
- mask face ? immobile + infrequent blinking) difficulty initiating movement
Rigidity (increased tone or stiffness in the muscles)
Postural instability (failing balance), walking problems (shuffling gait ..etc).
In addition the following manifestations may be present:
Autonomic: sexual symptoms, sweat,
constipation, and seborrhea.
Mental: slow thinking, mild dementia, and depression, anxiety or
Sleep disturbances, dizziness, altered sexual function,
fatigue, loss of sense of smell, oily skin, difficulty in swallowing.
State of reflexes in parkinsonism: deep
reflexes may be normal, increased or decreased.
Symptoms usually only begin to appear after about 80% of the dopamine
in the brain has been lost. The level of dopamine will continue to fall
slowly over time, with an attendant worsening of symptoms.
It is an incapacitating disease, disturbing some important human
functions and in some cases resulting in a substantial reduction in
quality of life. As in many neurologic diseases, psychological
complications are often extremely serious and require the patient's
family members and relatives to pay keen attention to the emotional
fragility that usually follows the emergence of the disease; indeed, the
depression which often results is seen by many as one of the worst
aspects of the disease. In some cases drugs are employed, especially in
the fight against depression (given that Parkinson's-related depression
is mainly induced by a complex of chemical-physical factors). Also, some
common side effects of therapy can put the patient in a condition of
humble self-consideration. External help is required to control the
administration of the prescribed therapy: since patients are often
confused or depressed, there is a risk of their improperly implementing
the therapeutic regimen if left to their own devices, leading to
symptoms not being adequately controlled.
The combination of bradykinesia and resting tremors is virtually synonymous
with the disease.
The treatment of Parkinson's disease mainly relies on replacing
dopamine with levodopa (L-DOPA) or mimicking its action with dopamine
agonists such as pramipexole, ropinirole, pergolide or bromocriptine.
Levodopa is a dopamine precursor that is transfomed into dopamine by the
brain). This is almost always supplemented with carbidopa, a drug which
prevents levodopa from being metabolized in the gut, liver and other
tissues, thus allowing more levodopa to reach the brain and allowing for
a reduced dosage, thus reducing some of the side effects. The most
frequent side effects of these dopaminergic drugs are nausea,
sleepiness, dizziness, involuntary writhing movements and visual
As in many other diseases, the therapy requires a continuing regimen
of medicines, the dosage of which has to be specifically calculated for
each single case and might vary during the evolution of the disease. The
treatment is complex and usually consists of a mixture of drugs
(basically focused on levodopa), some of which compensate for the side
effects of others. Amantadine hydrochloride, anticholinergics and COMT
inhibitors tolcapone or entacapone are sometimes prescribed. Foods rich
in proteins can reduce the uptake of levodopa, because the same uptake
system is used both by certain amino acids and levodopa. However, this
can usually be dealt with by redistributing meal times: in many cases it
is advisable to move the consumption of proteins towards the evening, so
to have symptoms appearing when the patient has less need of mobility.
While these therapies are a good attempt at treating the symptoms, they
are not a cure--they do not attack the underlying cause of the disease
which is a loss of dopamine producing neurons.
Regular physical exercise and/or therapy are beneficial to the
patient and essential for maintaining and improving mobility,
flexibility, balance and a range of motion, and for a better resistance
against many of the secondary symptoms and side effects.
Surgical interventions are currently being researched, and deep brain
stimulation is presently the most popular and effective such treatment.
In the future, implantation of cells genetically engineered to produce
dopamine or stem cells that transform into dopamine-producing cells may
Even these, however, will not constitute cures because they do not
address the widespread loss of several different types of cells in the
brain and even for the dopamine-producing cells, do not re-establish all
of the original connections with neighboring brain cells. A true cure
will have to detect the earliest signs of the disorder before they cause
important symptoms and will intervene in the process that damages the
brain cells in the first place.
In the early stages Parkinson's disease does not necessarily affect
intellectual integrity, apart from the emotional effects of eventual
psychological complications, and in those cases where the patient is
still compos mentis, their role in the treatment is fundamental. The
patient's cooperation is required in order to provide the physicians
with all the details that might help in the making a correct diagnosis
and consequent determination the best appropriated therapy. Conversely,
it is crucial for doctors to explain the precise extent of the disease's
progress, and provide as much information as possible about the
prescribed therapy, how the symptoms and side effects can be reduced.
Working together in this manner, the patient and doctor can ensure the
maximum quality of life for the sufferer.
N.B. side effects of L-dopa include depression,
confusion, GIT and palpitations and