Download Parkinson`s Disease

By Eamonn Brady MPSI
Parkinson's Disease
Parkinson's disease is a chronic (long-term) disorder of caused by the degeneration
of dopamine generating cells in the mid-section of the brain. The reason for this
degeneration in Parkinson’s patients still remains largely unknown. It mainly affects
the way the brain co-ordinates movements of the muscles in various parts of the
body. Symptoms gradually worsen over time. The main symptoms of Parkinson's
disease are stiffness, shaking (tremor) and slowing of movement. There is no cure
but treatment can slow down its progression and can provide good relief of
symptoms for several years in most patients. Modern treatment options means that
people with Parkinson’s can have a normal or near normal life expectancy.
Profile of patients
According to the Parkinson’s Association of Ireland, approximately 9000 people in
Ireland are affected by Parkinson’s. Parkinson’s usually develops in people over the
age of 50 and is rare in people under 50. It affects about 5 in 1,000 people in their
60s about 40 in 1,000 people over 80. Men are one and a half times more likely to
get Parkinson’s than women; the reason for this is unknown. Parkinson’s does not
seem to have a genetic link so it does not appear to run in families. There is some
evidence that there is a small risk of a hereditary link in those who develop it under
50. There is some evidence that smoking increases risk of Parkinson’s.
Causes
The substantia nigra region of the brain is the area affected. The substantia nigra
controls muscles in the body by sending messages via nerves in the spinal cord to
the rest of the body. Messages are passed between brain cells, nerves and muscles
via chemicals called neurotransmitters. Dopamine is the main neurotransmitter
produced by the brain cells in the substantia nigra. With Parkinson’s, cells in the
substantia nigra become damaged and die over time. As the cells die, the amount of
dopamine produced is gradually reduced.
Symptoms
The brain cells and nerves normally help to produce smooth, co-ordinated
movements of muscles. The gradual reduction of dopamine causes the three main
symptoms of Parkinson’s, slowness of movement, stiffness and tremor. The
symptoms of Parkinson’s often occur in one side initially (eg) tremor in one leg or
one hand, loss of ability to swing your arm or leg on one side. It is worth noting that a
reduced sense of smell may be one of the initial symptoms in early Parkinson’s.
Slowness of movement (bradykinesia). This causes difficulty performing simple
and legs tending not to swing as easily.
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Stiffness of muscles (rigidity) is when the muscles become tense with the arms
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everyday activities like walking, climbing a stairs or getting out of a chair. Many
people mistake this as a normal part of aging which means diagnosis is delayed in
many cases. Diagnosis often does not occur until other symptoms like tremor of
stiffness occur. With time, normal walking becomes difficult and Parkinson’s patients
often develop a 'shuffling' type of walk with difficulty in starting, stopping, and turning.
By Eamonn Brady MPSI
Tremor is common symptom of Parkinson’s. For many people it is the symptom that
leads them to seek treatment and thus allow diagnosis. However not all patients with
Parkinson’s have tremor. About 30% of Parkinson’s patients do not suffer from
tremor initially but it always develops as the condition progresses. It usually affects
the fingers, thumbs, hands, and arms, but can affect any part of the body. It is most
noticeable when resting. Tremors tend to worsen when anxious or emotional and
tends to reduce when using your hands or picking up an object or moving the
affected area.
The speed in which symptoms become worse varies from person to person. It can
take several years before symptoms become bad enough to affect routine tasks and
quality of life. In many cases one side of the body may be more affected than the
other initially but with time both sides are usually affected equally.
As the condition develops and more dopamine receptors are destroyed, other
symptoms develop. These include difficulty with balance and posture and an
increased tendency to fall. Further symptoms include inability to perform facial
expressions like smiling or frowning; reduced blinking; difficulty with fine movements
such as using a scissors, tying shoelaces, opening and closing buttons, zipping up
and difficulty with writing (handwriting tends to become smaller). There can be a
slowdown in speech leading to a monotone voice and swallowing difficulties can
develop leading to pooling of saliva in the mouth. Tiredness, aches and pains are
other possible symptoms.
Other symptoms which occur in some people as the condition develops include:
 Bladder symptoms including incontinence
 Constipation
 Sweating
 Sexual difficulties.
 Alterations in sense of smell
 Sleeping problems (can be disturbed sleep at night or excessive sleep during
the day)
 Hallucinations
 Weight loss
 Pain
 Depression
 Anxiety
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There is no specific test to diagnose Parkinson’s. Diagnosis is based the typical
symptoms. It may be difficult for diagnosis initially with many people not being
diagnosed for years after developing the condition as symptoms are mild and may
be mistaken as a normal part of aging. Parkinson’s is sometimes confused with other
conditions that have some “Parkinson” type symptoms. Parkinson symptoms may
occur in people suffering from neurological disorders such as Alzheimer's disease,
Huntington's disease, Wilson's disease, spinocerebellar ataxias and CreutzfeldtJakob disease (better known as “mad cow disease”). Other conditions that can
occasionally display symptoms similar to Parkinson’s include brain injury, brain
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Diagnosis
By Eamonn Brady MPSI
infections (such as encephalitis), hyperthyroidism, brain tumour, liver disease,
stroke, carbon monoxide poisoning and heavy metal (such as manganese)
poisoning.
Some medication can cause side effects that resemble symptoms of Parkinson’s. A
form of Parkinson’s which is reversible sometimes develops from some drugs such
as chlorpromazine and haloperidol, which are prescribed for patients with psychiatric
conditions. Some anti-sickness medication (metoclopramide) and epilepsy
medication (valproate) may also cause Parkinson type symptoms. Reducing the
dose of these medications generally eases or stops the Parkinson type symptoms.
A neurologist or a doctor specialising in elderly care usually makes the diagnosis of
Parkinson’s. While a scan of the brain cannot determine if Parkinson’s is present it is
sometimes used to differentiate Parkinson’s from other conditions that cause
Parkinsonism features.
Link between Parkinson's disease and dementia
The thinking part of the brain is not affected by Parkinson’s so dementia is not a
usual early feature. However, Parkinson’s increases the risk of developing dementia.
Approximately 40% of patients with Parkinson’s develop dementia but dementia
typically does not develop until 10 years or more after the first Parkinson symptoms
occur.3 If dementia occurs, it generally develops in Parkinson patients over 70. The
cholinesterase inhibitors rivastigmine (Exelon®), donepezil (Aricept®) and
galantamine (Reminyl®) have been shown in studies to have a modest benefit in
cognitive function and in the reduction of hallucinations and psychosis in patients
with Parkinson related dementia. Rivastigmine appears to be most effective for
Parkinson’s related dementia with donepezil to a lesser extent.
Treatment
While there is no cure for Parkinson’s, treatments can ease symptoms and slow
progression. If diagnosis is early, medication is often started before symptoms
become troublesome to slow progression.
Medication
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Levodopa
Levodopa tends to give a good improvement in symptoms. Levodopa is converted to
dopamine in the brain. The dose is started low but tends to be increased to control
symptoms. Levodopa is always used in combination with another medicine to
prevent side effects (either benserazide or carbidopa). Benserazide and carbidopa
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Scottish Intercollegiate Guidelines Network (SIGN) which is an influential health
guidance authority in the UK recommend starting with a dopamine agonist (ie.
levodopa) with a dopa-decarboxylase inhibitor or a monoamine-oxidase inhibitor.
There are other anti-Parkinson medicines available but they are not used as often as
the three types of medication described above but they can be used in addition to
these to improve response. Levodopa is considered the most effective Parkinson
treatment and is central to any pharmalogical treatment regime. It can take 8 to 10
weeks from the start of treatment before the patient notices improvement in
symptoms.
By Eamonn Brady MPSI
prevent levodopa being converted to dopamine before it reaches the brain thus
reducing side-effects. Levodopa combined with benserazide is called cobeneldopa
(Madopar®) and levodopa combined with carbidopa is called cocareldopa
(Sinemet®). Side effects from Levodopa tend to be rare at low doses. Nausea is the
most common side effect. Other side effects which may occur include vomiting,
dizziness and low blood pressure; however these often ease after a few days of use
and are minimised by starting with lower doses. Levodopa can occasionally cause
compulsive behaviour in some people (eg) urge to gamble, spend money. The effect
of Levodopa tends to wear off over time, usually over a period of 3 to 5 years.
Problems that occur with time include 'on-off' effects; thus alternating between being
'on' (being able to move freely), and being 'off' (not being able to move) in quick
succession. Another side effect can be dyskinesia which is uncontrollable jerky
movements which can be disabling, tiring and painful. Levodopa can cause other
movement disorders such as head nodding, jerking and twitches. Movement
disorders caused by Levodopa appear to come on quicker in younger patients
(under 60) than older patients. Keeping the levodopa dose at the lowest that is
effective to control Parkinson’s symptoms is the best way to reduce risk of
movement disorders.
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Despite being slight less effective than Levodopa, one potential advantage of them
as compared with levodopa is that their use is associated with at least a 50% lower
risk of dyskinesia (involuntary movements) and other movement type side effects in
the first four to five years of treatment, particularly among patients receiving
dopamine-agonists on their own. Many doctors prescribe dopamine agonists as the
first choice to delay the starting of levodopa as levodopa generally only works well
for about five years, thus the longer you can hold off using levodopa, the longer it
takes to get to the stage when it wears off. A dopamine agonist may be tried in
combination with levodopa as the condition gets worse. Apomorphine is an
alternative dopamine agonist that is used in combination with levodopa; it is
administered as a subcutaneous injection. It is only used when the condition is no
longer controlled by the main drugs used for Parkinson’s such as leovodopa and is
reserved for patients with severe 'off' episodes and immobility. As its effect wears off
after about an hour, frequent injections are therefore needed, thus it is sometimes
given as a continuous infusion. In trials comparing levodopa and dopamine agonists,
symptoms of Parkinson’s improved with levodopa by about 40 to 50% as compared
with approximately 30% with dopamine agonists.
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Dopamine agonists
Dopamine agonists mimic dopamine. There are several types. Ropinirole (Requip®),
pramipexole (Mirapexin®) and rotigotine (Neupro® patch) are used most commonly.
Bromocriptine (Parlodel®), cabergoline or pergolide are used less often because of
the risk of side effects which include thickening of heart valves and thickening or
scarring of lung tissue. Initial side-effects are similar to levodopa (nausea, vomiting
and dizziness) however side-effects tend to ease within a few days or weeks.
Drowsiness can also occur. Like Levodopa, compulsive behaviour can be a sideeffect; compulsive behaviour is more of a problem with dopamine agonists than
levodopa. Dopamine agonists should be avoided in the treatment of patients with
dementia because dopamine agonists can produce hallucinations.
By Eamonn Brady MPSI
Monoamine oxidase-B inhibitors
Sometimes used as alternative to levodopa for early Parkinson’s. They include
selegiline (Eldepryl®) and rasagiline (Azilect®). They work by inhibiting or blocking
the effect of monoamine-oxidase-B (MAOB) in the brain, a chemical that prevents
the breakdown of levodopa and dopamine. Blocking the effect of MAO-B means the
effect of dopamine lasts longer. Most Parkinson’s sufferers require levodopa
eventually when the disease gets worse. MAO-B inhibitors are sometimes used as
the first treatment after diagnosis as it can delay the requirement for levodopa for
months or years. MAOBs are often used in combination with levodopa as the
condition progresses.
Other medication used for Parkinson's disease
Catechol-O-methyltransferase (COMT) inhibitors have become available in the last
20 years. Entacapone (Comtess® and also an ingredient in Stalevo®) is a COMT.
COMT inhibitors are often given in combination to levodopa as it slows the
breakdown of levodopa by the body so a higher percentage of levodopa can get to
the brain to work. A COMT inhibitor is often added to levodopa when levodopa is not
controlling symptoms sufficiently alone or where the effect of levodopa wears off.
This is why Stalevo® has grown in popularity in recent years.
Other medicines are sometimes used to help relieve symptoms. These medicines
aim to correct the chemical imbalance in the brain. Examples include beta-blockers,
amantadine and anticholinergic drugs. However they are only a temporary or add on
therapy as levodopa or dopamine agonists are the mainstay and the most effective
therapies available for Parkinson’s.
Non drug treatment options
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Surgery
Surgery was not traditionally part of Parkinson’s treatment and is not still commonly
used as a form of treatment and techniques are still in the early days of
development. Surgery will not cure Parkinson’s but may help ease symptoms when
medicines are not working well. An example of a surgical procedure for Parkinson’s
is chronic deep brain stimulation, a technique that involves putting a pulse generator
(like a heart pacemaker) in the chest wall. Fine cables are placed under the skin;
they connect to electrodes placed in the brain. The electrodes stimulate parts of the
brain affected by Parkinson’s and can help to ease symptoms. Clinical trials are still
underway for this therapy as long-term safety of this surgery is not certain. Deep
brain stimulation is not yet available in Ireland and you must travel to the UK for
treatment with this technique under the HSE.
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Therapies
A physiotherapist can advise and help with movement. They will concentrate on
posture, walking and exercises, thus maximising the length the person can move
and manage independently. An occupational therapist can advise on areas that will
make the person’s day to day living easier to manage and will advise on home
adaptations and devices which can simplify tasks that become difficult due to the
condition. A speech and language therapist can help if difficulties with speech,
swallowing or saliva occur; these difficulties normally only occur later on in the
condition.
By Eamonn Brady MPSI
General advice
Stay as active as possible
Exercise regularly as much as you are able. Exercise may not be possible as the
condition progresses. Walking and movement may be slower than before, but
walking regularly can help loosen up stiff muscles and will help maintain and improve
balance which will make falls less likely.
Constipation
Constipation is common with Parkinson’s as the nerves which allow the bowels to
move freely are not functioning as well. Prevention includes staying well hydrated
and eating plenty of fruit and veg and high fibre foods. Exercise can also improve
constipation. Laxatives may be required as the disease progresses.
Side effects of medication
Familiarise yourself with any possible side effects of medication so you can
recognise them early and deal with them promptly if they occur. Speak to your doctor
and pharmacist about possible side effects and ‘Patient Information Leaflets’ that
come with the medicines are an important source of information. You should inform
your doctor or pharmacist of any side effects. For example, hallucinations, confusion
and mental changes are possible side-effects of some medicines used to treat
Parkinson’s.
Driving
Your doctor can advise you if driving is still possible. Depending on the severity of
symptoms and the medicines that you are taking, driving may still be possible
following a medical assessment.
Depression
Depression is thought to occur in approximately 40% of patients with depression.
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Psychosis
Psychosis may occur in up to 30% of patients with Parkinsons. It often presents as
hallucinations which are usually visual together with delusions and agitation or
occasionally aggressive behaviour. Paranoia may occur particularly towards partners
and family members. Psychosis is thought to be due to the loss of dopamine
receptors in the substantia nigra region of the brain. Older “typical” antipsychotics
such as chlorpromazine (Clonactil®, Largactil®) and haloperidol (Serenace®) can
worsen symptoms of Parkinson’s including movement and should be avoided. The
newer “atypical” antipsychotic agents such as quetiapine (Seroquel®) and clozapine
are better tolerated and often effective in controlling psychosis. Close monitoring of
the white cell count is important with clozapine because of a 1% chance of a serious
condition called agranulocytosis (a loss of the white blood cells which reduces the
ability to fight infection). Acetylcholinesterase inhibitors such as the anti-Alzheimer’s
drugs rivastigmine (Exelon®), donepezil (Aricept®) and galantamine (Reminyl®) may
also be beneficial in reducing hallucinations and delusions in Parkinson patients.
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The main reason for depression is the massive impact Parkinson’s can have on day
to day living and life expectancy. Depression can cause symptoms similar to
Parkinson’s and which may make it look like Parkinson’s is getting worse when
actually it is not (such as lack of energy and becoming slower).
By Eamonn Brady MPSI
Practical tips
Limit caffeine intake as caffeine can act as a diuretic and increase the frequency of
urination. Decrease fluids to either two hours before bedtime, after dinner or earlier;
this will reduce waking up at night to use the bathroom. Sleep deprivation can
exacerbate symptoms of Parkinson's. At night, a portable urinal and or bedpan can
be an alternative to getting out of bed to make trips to the bathroom which can be
difficult. Using a shower stall is much easier and much safer than a shower/tub
combination. The shower area should be fitted with at least two handrails.
It is easier to get up from a high chair than from a low couch. Consider using Velcro
fasteners instead of buttons; carrying a walking stick when out can increase
confidence if unsteadiness is a problem. Use an electric toothbrush and razor to
make brushing your teeth and shaving easier. There are many utensils designed for
people living with disability which can make everyday chores like eating, preparing
food easier, grooming and cleaning easier. Examples include reaching devices,
electric jar openers, modified cups and utensils for ease of holding and use, the list is
limitless. Ask your occupational therapist or pharmacist for more details.
Longer term outlook
Symptoms tend to get worse with time but the speed of progression may vary
significantly from person to person. Many do not need treatment initially as
symptoms may be relatively mild. Most Parkinson’s sufferers have a period of
relatively mild symptoms. When symptoms become worse, medication can give
several years of good or reasonable control of the symptoms. It is difficult to predict
how quick the condition will progress. Some people may only have mild symptoms
20 years after diagnosis with other being disabled after only 10 years.
Parkinson’s Association of Ireland
The Parkinson’s Association of Ireland provides support for Parkinson’s patients,
their families, carers and healthcare professionals. They operate a Freephone
number (1800 359 359, Monday to Friday 9am to 9pm), they have a nurse on staff,
provide free information leaflets and organise regular information evenings around
Ireland. They also operate 14 branches around Ireland which operate on a local
basis and are run by volunteer committees. The closest branch to Westmeath is the
East Midlands branch; you can contact Marian Deely from the Midlands East branch
at 045 435023. If you or a loved one is affected by Parkinson’s, they can be a great
source of information and support.
References
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Psychiatry. 2004;75:637-9
3. Davie, C.A. A review of Parkinson’s disease. British Medical Bulletin. April
2008; 86: 109–127
By Eamonn Brady MPSI
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