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Family
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Preview of Understanding Parkinson's Disease
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The essential cause is
not known. Clues are available from studies of the distri-bution of the
disease, that is, who is affected, where and in what circumstances. These
show associations that don’t prove a cause, but lead to the investiga-
tion of possible causal or contributory factors, which may play a part
in causing the illness. I have already mentioned that it is relatively
common – perhaps as many as 100,000 patients are affected in the
UK at any one time – that men and women are equally affected, and
that no race is immune. It is not related to any particular job and is
clearly a physical disease of the brain, which is not caused by stress,
anxiety, emotional or family upsets. Extensive searches for a viral or
bacterial cause have proved negative, so the disease is not infectious.
Nerve cells in the brain are affected
In patients with Parkinson’s disease, there is
disease or degeneration of the so-called basal ganglia in the deeper
grey matter of the brain, particularly of that part known as the substantia
nigra.
The substantia nigra, which connects with the striatum
(caudate nucleus and globus pallidus), contains black pigmented cells
and, in normal individuals, produces a number of chemical transmitters,
the most important of which is dopamine. Transmitters are chemicals that
transmit, that is, pass on, a message from one cell to the next, either
stimulating or inhibiting the function concerned; it is like electricity
being the transmitter of sound waves in the radio. Other transmitters
include serotonin, somatostatin and noradrenaline. In Parkinson’s
disease, the basal ganglia cells produce less dopamine, which is needed
to transmit vital messages to other parts of the brain, and to the spinal
cord, nerves and muscles.
The basal ganglia, through the action of dopamine,
are responsible for planning and controlling automatic movements of the
body, such as pointing with a finger, pulling on a sock, writing or walking.
If the basal ganglia are not working properly, as in Parkinson’s
disease patients, all aspects of movement are impaired, resulting in
the characteristic features of the disease – slowness of movement,
stiffness and effort required to move a limb and, often, tremor.
Dopamine levels in the brain’s substantia nigra
do normally fall with ageing. However, they have to fall to one-fifth
of normal values for the symptoms and signs of parkinsonism to emerge.
In
Parkinson’s disease, there is degeneration of the substantia
nigra which produces the chemical dopamine deep inside the brain. |
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An important balance
Normally, there is a balance between dopamine and another
neurotransmitter – the transmitter of nerve impulses – called
acetylcholine. Acetylcholine is present in many areas of the brain and
plays a part in normal memory recording and recall. As dopamine is depleted,
there is a relative excess of acetylcholine. Thus two of the main groups
of drugs used to treat Parkinson’s disease are dopamine drugs (levodopa
and its preparations Madopar and Sinemet) and drugs designed to restore
the balance by diminishing the acetylcholine – anticholinergics
(for example, benzhexol [Artane], orphenadrine [Disipal] and benztropine
[Cogentin]).
How do the nerve cells send messages?
The diagram on page 6 shows how the nerve cells or
neurons in the basal ganglia release packages of the dopamine, transmit
it down its main wire or axon, and how this sprouts into receptors of
the next nerve cells and transmits the message and nerve impulse further
down the line. You can imagine this process carried out by millions of
neurons at the same time, forming a network of activity which puts BT
and other telephone networks to shame.
Current ideas about the cause of Parkinson’s disease
suggest a predisposition that makes certain people more vulnerable to
some (unidentified) environmental toxic agents. Why cells die in the
substantia nigra of Parkinson’s disease patients is unknown. This
important group of cells shows three changes:
- Evidence of the release of oxygen compounds by
cells which act as a stress that damages cells (oxidative stress),
and depletion of a chemical called reduced glutathione.
- High levels of iron.
- A deficiency of an essential component of all cells
(mitochondrial complex I) that normally controls oxidative reactions;
these last involve the release of oxygen compounds which act as stress
causing damage to the cells.
- Which of these is the primary event, causing
secondary changes culminating in death of the nigral cells, is not
known. In people with Lewy bodies in their brains but before the
development of symptoms of parkinsonism, the substantia nigra shows
a comparable loss of reduced glutathione and, possibly, a reduction
of complex I activity. Lewy bodies are small areas in nerve cells
(inclusions) present in practic- ally every case. They are pink acidophilic
(acid-loving) blobs, and show a central core with a peripheral halo.
As they may be signs of very early disease, before definite signs
emerge, these various abnormalities provide a new focus for the development
of future treatments.
Various
parts of the nervous system combine to generate movement. Nerve
impulses start in the cortex, pass through the basal ganglia,
brain stem and spinal cord, and finally pass through the peripheral
nerves which actually control muscles. |
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Receptors are important
The receptors are most important. Some drugs can block
the receptors, and if they are taken for a long period they block the
passage of dopamine in the nerve cells and their connect- ing network
of axons. The nerve impulses so essential for normal movements are therefore
reduced. This is the basis of the drug-induced parkinsonism I shall describe
next.
Ageing and heredity
Although Parkinson’s disease is not caused by
the normal ageing process that affects all our brains, just as it does
other organs, the incidence of the disease does increase as we get older.
The possible role of a genetic abnormality and of hereditary transmission
is one of the fertile areas for present and future research. A weak link
has been found between Parkinson’s disease and Alzheimer’s
disease, but genetic studies have ruled out any important connection.
Nor do the results support any role for genetic factors in the dementia
sometimes associated with Parkinson’s disease. A family history
is obtained in five to ten per cent of patients, but studies on twins
suggest that hereditary factors are relatively unimportant. It may be
that affected relatives share some environmental agent or are genetically
vulnerable to it. What this environmental factor might be, we do not
know.
Dopamine
is released from storage granules in the nerve cell, and travels
down the axon across the synaptic knob to dopamine receptors
at the next nerve cell. |
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KEY POINTS
- The cause of Parkinson’s disease is unknown
- Research has shown that pigment-containing cells
in the deep part of the brain that produce dopamine and other important
chemicals degenerate and die. This, in turn, affects the working
of other parts of the brain, the spinal cord, nerves and muscles
involved in movement
- When the chemical dopamine is depleted, there
is a relative excess of the chemical acetylcholine
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