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Parkinson’s disease
Dartington 26 June 2003
What is Parkinson's disease?
Parkinson's disease is a degenerative
disease of the nervous system
associated with trembling of the arms
and legs, stiffness and rigidity of the
muscles and slowness of movement
(bradykinesia).
What causes
Parkinson's disease?
It is caused by the progressive loss of neurones
in the substantia nigra, which produces the
chemical dopamine. As the cells die, less
dopamine is produced and transported to the
striatum (co-ordinates movement). Parkinson's
sufferers may also lack other brain chemicals
including serotonin (linked to mood),
noradrenaline (linked to blood pressure control)
and acetylcholine (linked to mental state).
Who is affected?
Parkinson's affects 8000-10,000 new
people in the UK each year.
On average one person in every 500 is
affected by Parkinson's disease.
Most patients are over 40 and it very
rarely affects people below this age
(only 5 per cent).
The risk rises so that by the age of 80
more than two people per 100 of the
population have developed some signs
of the condition.
What are the
symptoms?
The main symptoms of Parkinson's are:
tremor, usually while resting.
stiffness and muscle cramps (rigidity), particularly
affecting the arm, leg and neck.
slowness in initiating movement (bradykinesia)
Poor balance and unstable walking (shuffling,
difficulty in turning, falls).
Other symptoms
include:
expressionless face
reduced manual dexterity
handwriting difficulties
drooling
sleep problems
urination at night
depression and anxiety
constipation
difficulty in turning in bed at night.
How does the disease
progress?
Early signs include stiffness of fingers or
a stiff shoulder accompanied by
stiffness of muscles. Pain may be a
feature. Symptoms usually only affect
one side of the body for one to two
years and then spread to the other.
Tremor is often noticed first.
How is a diagnosis
made?
Differential diagnoses
Multi-system atrophy (MSA), corticobasal
degeneration (CBD), vascular pseudo-parkinsonism
and progressive supranuclear palsy (PSP), diffuse
Lewy Body disease, may all appear similar to
Parkinson's disease.
Where tremor is the main symptom, Parkinson's may
be confused with essential tremor (ET). In this
condition, tremors occur during activity rather than
during rest.
Several medications may also cause symptoms similar
to Parkinson's (antipsychotics and anti-emetics).
Treatment
Levodopa
Levodopa remains the 'gold-standard' treatment for
Parkinson's. Most patients notice an improvement
almost immediately.
Short-term side effects are uncommon but include
nausea, hallucinations, tiredness and lightheadedness. Virtually all patients suffer long-term
complications, with about 50- 75 per cent on the
drug for 5-10 years developing abnormal excessive
and involuntary movements called dyskinesias.
Dopamine agonists
These drugs include bromocriptine, lisuride, pergolide,
cabergoline, ropinirole, pramipexole and apomorphine.
They are less effective at controlling symptoms than
levodopa, particularly in advanced Parkinson's disease.
Patients are advised to take an anti-sickness tablet
(domperidone) for at least the first two weeks of
treatment.
The side effects of dopamine agonists are similar to
levodopa although nausea and mental problems such as
hallucinations usually occur more often.
Apomorphine
Usually administered under the skin by
injection or via an infusion pump over
12, 18 or 24 hours.
The main side effects are the formation
of skin nodules, nausea, yawning and
drowsiness. Apomorphine is usually
reserved for patients in whom oral
treatment is no longer effective.
COMT inhibitors
Catechol-O-methyl-transferase (COMT)
prolongs the beneficial effect of
levodopa. Two COMT inhibitors exist,
tolcapone and entacapone. However,
tolcapone is not in use in many
countries including the UK as it may
rarely cause severe liver toxicity.
Entacapone is available in the UK and is
usually used when the effect of
levodopa starts wearing off.
Other drugs I
Selegiline
A report by the Parkinson's Disease Research
Group of the UK suggested a 60 per cent increase
in mortality among patients treated over a long
period of time with selegiline. This has not been
found in other studies and a recent study from
Scotland has suggested that selegiline therapy
does not increase mortality in Parkinson's.
Side effects include hallucinations, sleep disorder,
agitation, postural hypotension.
Other drugs II
Amantadine
Amantadine is a mild antiviral agent and used in
young patients to delay the need to use
levodopa. In high doses, amantadine can act as
an anti-dyskinetic drug. Amantadine can cause
visual hallucinations, confusion and agitation. It
should be given as a single dose in the morning
to prevent sleep problems. It can cause livido
reticularis.
Other drugs III
Anticholinergics
Common anticholinergics include benzhexol,
procyclidine, benzatropine, orphenadrine and
biperiden. Used with levodopa therapy, they can
help control resting tremor and dystonia. In
older patients they may cause confusion and
aggravate dementia. Other side effects include
difficulty in passing urine, constipation, blurred
vision, dry mouth and the onset of narrow angle
glaucoma.
Other non-drug
treatment
Physiotherapy and speech therapy can
also help patients to manage their
symptoms and enjoy a better quality of
life. A dietitian can also advise on better
nutrition to avoid constipation.
Depression, sleep problems and urinary
difficulties are common in Parkinson's
and may need specific treatment.
Surgery
Brain surgery, to the pallidum, the
thalamus, and sub-thalamus, has been
shown to reduce symptoms in some
patients. Operations may involve
lesioning (destroying cells in a target
area by burning a hole), stimulation
(electrically stimulating cells using a
pacemaker) or transplantation.
Pallidotomy
In this operation a group of nerve cells
in the pallidum are destroyed. It is
particularly effective for treating
involuntary movements (dyskinesias)
and is relatively widely available.
However, operations on both pallidum
may cause severe side effects such
inability to speak properly and memory
difficulties.
Subthalamic deep
brain stimulation
This operation involves putting an
electrode into the subthalamic nucleus.
The stimulation can be controlled by the
patient using a switch that can turn the
stimulator 'on' or 'off'. This operation is
effective at controlling all the features
of Parkinson's but the procedure is
complex. Operation can be safely
performed on both subthlamic nucleii,
unlike pallidotomy.
The benefits of deep brain stimulation
include the fact it is not necessary to
make a lesion in the target and
stimulation can be adjusted if
necessary. However, the pacemaker
battery has to be replaced under
anaesthetic and the procedure is
extremely expensive and is only
available at some regional centres in
the UK.
Diagnostic red flags for IPD
?
Diagnostic red flags for IPD
Lack of tremor (PRRT)
 Symmetry
 Early balance problems
 Early cognitive problems
 Dopa unresponsiveness
 Pyramidal or cerebellar signs
 Supranuclear gaze palsies

Treatment decisions
1.
2.
3.
Elderly
Younger
Intermediate
When Specialist referral?
The confused PD patient on
multiple medications
Parkinson’s specialist nurses
Plymouth
Cory Wroath
Torbay
Andrea Ford
Dementia
The development of multiple cognitive deficits
that include memory impairment and at least one
of the following:
Aphasia
Apraxia
Agnosia
Disturbance in executive functioning
Differential Diagnosis
Alzheimer’s Disease
 Parkinson’s Plus Synd. - CLBD/PSPCBD
 FTLD
 Vascular Dementia
 Prion disease
 Others – MS/NPH/Whipple’s

Investigations for dementia
Bloods
 Neuropsychometry incl MMTS
 Neuroimaging
 EEG
 ?LP

Longitudinal assessment