The following report was made by the Danish
students:
Charlotte Egeboe,
Vibeke Grauenkj r
Ingun Hansen,
Vibeke Qvale Nyrud, and
Lars Frandsen.
They are all students (for the masters degree in
pharmacy) at the Royal Danish School of Pharmacy.
The report was received and accepted by me on
November 4, 1994.
As an educational experiment, these students
subscribed to the PARKINSN list. All of us are grateful
to the list owner and to the list members that you
allowed us to follow your discussions. Thank you !
Next week we will write you a letter to say good by
and then the Danish students will unsubscribe and
their e-mail address will be cancelled. I will stay on
the list, and the students can of course be reached
through me.
Best wishes to all of you...
Erling Sonnich Thomsen, supervisor,
associate professor, Ph.D.
November 11, 1994.
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***********************************
Parkinsons Disease - from the patients point of view
1. Summary.
This paper deals with Parkinsons Disease (PD) seen
from the patients point of view.
We start by describing the main symptoms of the
disease, which are resting tremor, muscle-rigidity,
bradykinesia, facial mask, slow blinking rate,
hypophonia, shuffling gait etc. Then we write about
the different kinds of treatment and the side-effects of
these.
We have focused on the use of anti-oxidants and
magnetic field therapy in the section of alternative
treatment and on pallidotomy in the part dealing with
surgical treatment.
2. Introduction.
Parkinson's Disease (PD) was named after the
English M.D. James Parkinson, who in 1817 was the
first person to describe the symptoms of the disease.
More than a century later, one has been able to point
out the cause of the disease, which is a dopamin-
deficiency in the basal ganglia of the brain.
The average age of getting PD is 57,3 years.
However there is about 5% of the PD-patients, who
get the disease before the age of 40.
It is estimated, that 1% of the population above 50
years old (in the US) suffers from PD. The reason of
the lack of dopamin is still unknown, but some
scientists believe, that environmental factors may
have an impact on the development of PD.
In this paper, we have focused on the social aspects
of the disease, and how the patients function in their
daily life.
The treatment and side-effects are of course of great
concern to the patients. Therefore we have also
written special sections about symptoms, medical and
alternative treatment, pallidotomy and side-effects.
Our main source of information has been the E-mail
list. Through this list we have been able to
communicate with people interested in the disease
from all over the world.
3. Symptoms.
PD is a progressive disorder of movement, that
occurs most commonly in elderly people. The main
symptoms are :
- Tremor at rest, usually starting in the hands, and
resulting in "pill-rolling" movements, which tend to
diminish during voluntary activity.
- Muscle rigidity, which is detectable as an increased
resistance in passive limb movement (bradykinesia)
- Inclination when standing (Postural instability. The
result is an abnormal center of gravity, which may
lead to rapid short-stepped walking.)
- Decrease in frequency of voluntary movements
(hypokinesia), which is partly the result of muscle
rigidity. But also partly due to an inherent interia of the
motor system, which means that motor activity is
difficult to stop as well as to initiate (Akinesia)
One of the earliest and most obvious symptoms is a
progressive resting and postural tremor, which is
absent during voluntary movements. Tremor is
experienced by 85% of all PD-patients (US). The
extremities, and sometimes the face, lips and chin are
usually involved in tremor.
Some patients have reduced voice-volume and
problems with speaking (hypophonia).
Tremor increases with frustration, anxiety and stress,
but tremor usually subsides during sleep.
PD-patients show a characteristic fast shuffling gait
(festinating gait), which takes some effort for them to
stop or change direction.
PD is commonly associated with dementia; the
patient experiences personality disintegration,
confusion and memory loss.
Because of the hypokinesia, PD-patients have
difficulties with handwriting, which has some obvious
characteristics; the letters get smaller and smaller. As
the disease progresses, the patient become unable to
write.
Not only old people get PD, some develope the
disease younger than 40 years of age. This group of
young patients (early on-set) experience the disease
in a different way than the late on-set-patients. The
young patients tend to have a better balance and
walking. They do not experience as much dementia as
the late on-sets, they tend to have fewer problems
with thinking and memory. They have more tremor
and sometimes, they have more involuntary
movements and they seem to tolerate the medication
better and get fewer side-effects.
(ref.: 9 & 15)
4. Treatment.
4.1 Medical treatment.
Going through therapeutical groups :
4.1.1. Levodopa :
This is the most important drug in the
treatment of PD. Levodopa (or L-dopa) is a precursor
for dopamine, while L-dopa can pass the blood-brain
barrier, dopamine cannot.
L-dopa is absorbed in the small intestine and
converted to dopamine by the enzyme dopa-
decarboxylase. This enzyme is widespread in the
peripheral tissue, and approximately 95% of the L-
dopa is here converted to dopamine. Only about 1%
enters the brain, where it is converted to dopamine. It
is due to the small fraction of administrated drug
absorbed, L-dopa has to be given in large and
frequent doses - up to 3-8 g/day in about 3-4 doses.
Unfortunately the effect of levodopa tends to
decline as the diasease advances, and the patient
needs larger and larger amounts of drugs, which
cause the side-effects to increase.
4.1.2. Levodopa in combination with decarboxylase-
inhibitor :
There are two kinds of medication available in
Denmark with two different decarboxylase-inhibitors :
Sinemet (Carbidopa) and Madopar (Benserazide).
The decarboxylase-inhibitors (DCI) do not pass the
blood-brain barrier and therefore only inhibits the
convertion of levodopa in the peripheral tissues. This
means, that a greater fraction of drugs enters the
brain and reduces the dose of levodopa needed (four
to eight-fold). This again reduces the peripherically
side-effects. These types of drugs (especially
Sinemet) are the most commonly used drugs today.
A lot of patients are taking Sinemet tablets (not
controlled release) dissolved in orange juice. The
vitamine C keeps the L-dopa from oxidizing and the
effect occurs more rapidly.
4.1.3. Mono-amino-oxidase B-inhibitor (MAO-B-
inhibitor) :
The enzyme MAO-B decomposes dopamine.
This means, that a MAO-B-inhibitor (Selegiline) can
help maintain a certain amount of dopamine in the
brain (whether the dopamine is produced in the brain
or taken orally).
Many trials has also shown, that Selegiline
possibly has a protective effect i.e. a delay in
progression of PD.
The only product sold in Denmark is Eldepryl
(ORION)
"Actions of Selegiline at different dosages
include : MAO-B-inhibition, dopamine re-uptake
inhibition, reinforcement of defuse against "oxidative
stress" and substitution for trophic factors."
(ref.: 15)
4.1.4. Acetylcholine (Ach.) antagonists.
These drugs were the main form of treatment,
before levodopa was discovered
Muscarine Ach. receptors exert an excitatory
effect, opposite to that of dopamine and also exert a
presynaptic inhibitory effect on dopaminergic nerve
terminals. Suppression of these effects by the Ach.
antagonists, thus makes up, in part, for a lack of
dopamine.
Ach. antagonists have a better effect on tremor
that on rigidity and hypokinesia. The side-effects are
very common and Ach. antagonists are now used for
patients, who respond poorly to levodopa.
There are several Ach. antagonist preparations
on the Danish market, for instance Artane
(benzhexol), Atropin (atropin) and Cogentin
(benzatropin).
4.1.5. Amantadine.
There is still much doubt about the mechanism
for the action of Amantadine. But it has been
suggested, that it increases dopamine release and
thus act like a dopamine-agonist.
Amantadine is less effective than levodopa and
bromocriptine, and the action tends to decline with
time, often after just a few months.
In Denmark the only preparation on the market
is Virofral (Novo).
4.1.6. Bromocriptine.
Bromocriptine stimulates dopamine-receptors,
and thus act like a dopamine-agonist. It is very similar
to levodopa and has almost the same side-effects.
Bromocriptines duration of action is longer (plasma
half-life 6-8 hours) than levodopas, so it does not
have to be given so frequently.
The drug tends to be used either in the first
stage of PD, as a supplement to levodopa, or for
patients whose responds to levodopa is
unsatisfactory.
(ref.: 8, 9, 11 & 15)
4.2. Pallidotomi
The tremor associated with PD is caused by the
dopamin-deficiency in the brain. Dopamin stimulates
the inhibitory nervefibers in globus pallidus of the
brain. When these inhibitory nervefibers are not
stimulated, an increased electrical activity in the
motoric center of the brain is created.
Scientists have recently discovered, that by
cutting pallidofugal fibers the abnormal stimulation
from the globus pallidus to the thalamus (and thereby
tremor) is reduced.
The surgery is only performed by a few
specialists. A probe is inserted through a hole in the
skull to the target location; globus pallidus. The tip of
the probe is heated to cause lesions of the
pallidofugal fibers. The patient has to be conscious
during the surgery to be able to communicate with the
surgeon.
Most operations have been succesful. The
result have been an improvement in tremor and
rigidity, which are the most hampering symptoms.
Other benefits may be reduced drug (L-Dopa)
requirements and improved mental well-being. But
unfortunately some side effects have been reported.
Increased bradykinesia is the most common. Others
are scotomas in the visual field and foot apraxia. The
benefits of pallidotomi sometimes tend to fade away
after some time (years). Despite of this, the
improvement, the patient feels after surgery, is of
great importance.
In Denmark pallidotomi is still considered
experimental. No Danish surgeons perform
pallidotomi, and the patients have to pay the
expences themselves. In the US and Sweden
pallidotomi is accepted as a surgical treatment, and
the insurance covers the operation. Although
pallidotomi has been a great help for some patients,
others are more sceptical about it and do not
recommend it, unless all other treatments fail.
(ref.: 15)
4.3. Alternative treatment
It is logical that people, who are suffering from
an incurable disease, often tries alternative treatment.
Some of the kinds we have met includes antioxidants
(Vitamin C & E, Q10 etc.), herbs, ginseng,
acupuncture, yoga and physiotherapy.
There is much doubt about the effect of the
medical treatment. There have only been made a few
trials of the alternative drugs, and often the
documentation of the effect is very poor. We have
chosen to focuse on antioxidant treatment; this is the
subject, we find the most interesting.
Endogenous enzymatic oxidation and non-
enzymatic autooxidation in monoamine neurons leads
to the formation of free radicals, which damages the
cells. This means, that the cells cannot produce
enough dopamine to keep up the normal level.
One trial, which came out with interesting
results, was one made by S. Fahn MD. His hypothesis
was to see whether high dosages of antioxidants
could slow the process of increasing the scavenging
of free radicals in the brain. His results is measured in
month of PD before levodopa was necessary.
Compared with a control group (no treatment with
antioxidants), the time when levodopa became
necessary, was extended by 2.5 years in the group
taking antioxidants.
We have included physiotherapy in this
section, although you may not call it alternative.
Almost everybody we have been in contact with, tells
about progressing after physiotherapy; less rigidity
and bradykinesia and a better and safer walk.
We have encountered different points of view,
whether yoga and acupuncture seems to help the
patients.
Magnetic field (MF) therapy has also been
tried in treatment of PD. Reuven Sandyk have made a
study of the effect of MF in parkinsonian patients. A
summary theory of MF-therapy would be: The pineal
gland is impacted by the magnetic fields, and
melatonin ( a neuro-transmitter) secretion are
inhibited. Melatonin is thought to inhibit dopamine
production, therefore its inhibition would improve
dopamine production. The treated patients experience
mood elevation, less fatigue, clearer and louder
speech, diminished tremor, better handwriting, better
facial expression and more normal gait. The
improvement of the symptoms last for 3 to 4 days. It is
not clear, whether there are side-effects, or how the
patient will respond to long-term treatment.
(ref.: 4, 5, 7 & 12)
5. Side effects
All medicines have their side effects. The more
drugs a patient uses, the more pronounced the side
effects become.
The medical treatment of PD is associated with
difficulties in finding the right size of the dosis : Too
small doses give elevated PD symptoms, and too high
doses cause side effects.
5.1. The main side effects related to anticholinergic
anti-PD drugs such as Atropin and Artane are :
- lack of saliva in the mouth
- difficulty in focusing at different distances
- tachykardia (elevated heart frequency)
- retention of urine
- gastro-intestinale inconveniences
- loss of appetite
- nausea
Symptoms from the central nerve system (CNS) are
- dizzyness
- sleepyness
- confusion (especially felt by elderly)
5.2. Some PD-patients use Bromocriptine in addition
to Sinemet, which also gives side effects such as :
- nausea
- vomiting
- dizzyness
- headache
High doses of Bromocriptine give hallucinations
(this is due to the drugs chemical simularity to LSD),
feeling of confusion, hypotension, light obstipation,
restless legs syndrome and dry mouth.
Young patients tolerate Bromocriptine better
than older patients.
More rare are side effects such as pale fingers
and toes, when they are cold, as well as pleuro-
pulmonal changes.
5.3. Levodopa in combination with decarboxylase-
inhibitors (Sinemet / Madopar) :
The active drug Levodopa, is somewhat
metabolised in the body, before it is transformed to
dopamine in the brain. It is these metabolic products,
that gives many of the unwanted side effects. To
reduce the metabolism of Levodopa decarboxylase-
inhibitors are added to the drug.
The main side effects are :
- loss of appetite
- nausea
- vomiting
- low bloodpressure (which in upright position
causes dizzyness and fainting)
More rare are tachykardia (increased heart
frequency) and palpation.
Mental side effects such as :
- euphoria
- irritation / aggressiveness
- inner inconvenience
- sleeping problems
- nightmares
- depression
- confusion
- hallucinations
5.4. Mono-amino-oxidase B inhibitors (Eldepryl).
The most common side effects are :
- dyskinesia
- nausea
- dizzyness
- confusion
- sleeping problems
- hallucinations
Mixing of Eldepryl and Levodopa may cause
severe hypotension.
5.5. Amantadine.
Most of the side effects from Amantadine are
the same as for a lot of the other drugs. But there are
also two very characteristic side effects from the drug.
These are :
- bluecolouring of the skin on the legs (livedo
reticularis)
- oedema on the ankles
(ref.: 1, 8, 10, 11 & 15)
6. Social aspects
As with all other incureable diseases, the PD-
patients have difficulty in accepting their situation. It is
hard to change lifestyle, when you have been living a
normal life for so many years. Many patients find it
difficult to tell family and friends, that they have PD,
because they are afraid of being treated like a sick
person; they don't feel that handicapped. The fear of
being rejected also makes it diffiicult to tell the
collegues at work about the disease. And of course
there is also a fear of being fired.
The young PD-patients are very conserned
about, whether they will be able to keep their jobs or
not. The young patients do often have a family to
support, and without a job, they will get financial
problems. Some young patients have been forced to
retire prematurely. There are psychological factors
related to job loss that go beyond financial
considerations.
It demands a great deal of both understanding
and patience from the surroundings, especially from
the family. Simply daily routines like getting dressed,
pouring a cup of coffee, going to the bathroom etc.
becomes a problem. Support from the family, both
mentally and psychologically, are of great importance.
To strengthening one self physically, seeing a
physical therapist is a great help. It is important to
move your limbs and use your muscles in order to
remain mobile and not get stiff. If the patient does not
use his body and exercise, his muscles and joints
becomes stiff and he/she feels pain when moving
around. Regular exercise helps the patient physically,
so he/she can better do the daily routines.
In Denmark the patient has to pay for the
physical therapist themselves. This is very strange,
because other comparable diseases to PD, will have
the treatment paid. The Danish PD-organization is
working on this problem.
Even though all these physical problems;
bicycling, skiing, playing the piano etc. may not cause
difficulties for some. Going on a bikeride or playing a
melody on the piano, may feel very encouraging to the
patient.
Some also change eating-habits. Overweight
can be a problem, because of the weakening of the
muscles - it increases the immobility. High-protein
food delays the absorption of L-Dopa from the
intestine and thereby the effect of the medication. This
is why many change to a healtier diet with more
vegetables and less meat.
In coping with all these new changes, the
patients can often feel exhausted and depressed. The
depression can also be induced by the medicine. In
this situation it is important, that the patient keeps the
spirit and does not isolate.
Because af psysical symptoms many find it
difficult to socialize. They fell like people are staring at
them, and giving them to much compassion. Some get
easily tired of constantly controlling their movements
and speaking clearly. It is so much easier to stay at
home with people you know and without any fuss.
One of the symptoms of PD is problem with
speaking. Their problem of comunicating makes it
hard and sometimes impossible to take part in
discussions. The feeling of being left out the
conversation and not beingt able to reply fast enough
is frustrating. They have their opinions, but they just
can not express themself. Not only in speech but also
in writing. It must be very frustrating not even being
able to write a letter on a computer - this is of course
a problem related to the last stages of the disease. All
these things can make the patient feel intellectually
disabled.
A good thing in this situation is to have a
neurologist that understand your problems, and who
can give you good advise and support. Unfortunately
not all patients have such a good relationship to their
neurologist. They seek support and understanding
other places.
Some PD-organisations have established
support-groups for their members. Here they talk
about their problems and get good advises from other
members. In Denmark the PD-organisation arrange
trips for their members to warm contries, and other
social arrangements.
In the early stages of the disease the
symptoms may not be that pronounced, so the patient
does not feel the need to seek the support-group.
He/she will rather try to function normally in the daily
life. The support-group may be more important to the
family. As the disease progresses, the need for
support from others in the same situation becomes
more important.
An alternative to support-groups is the E-Mail
net. Through this list you can communicate with
patients, relatives, specialists and other people
interested in PD. Here you can get information about
new treatments, references to specialists, discuss
experiences related to PD and make new friends. At
the same time, you can get encouraged by others with
the same problems, and you feel like all the others
care for you and try to help you in every possible way.
Through the list you can also get information about all
kinds of treatments. This is of course of great interest
to the patients, as the medicine gradually loses its
effect. The patients are interested in all kinds of
treatments from hypnosis to magnetic fields, and there
are always someone on the list, who can give more
information about the topic. It is not hard to
understand, that the patients try everything possible to
ease their symptoms. Even though they are living with
an incurable disease, which strongly affect their daily
life - they try to function as normal as possible.
(ref.: 1, 2 & 15)
7. Conclusion.
The common knowledge about PD is in
Denmark very limited, even though there are 6000
patients (out of a population af 5.2 million). This might
be because mainly old people are affected by the
disease, and the fact that only half of the patients are
members of the Danish Parkinsons Organization.
Our impression is that many PD-patients tries
to hide their illness, but at the same time have a very
strong need for social support and encouragement.
8. References.
1) Dupont, E., Parkinsons sygdom og dagligdagen,
Roche A/S, 1987
2) Ek, B., Balancegang, Dansk Parkinsonforening,
1991
3) Fahn, S., An open trial of high-dosage antioxidants
in early Parkinsons Disease, American Journal of
Clinical Nutrition, Jan. 1991, 53 (1 Suppl) : 380S -
382S
4) Fahn, S., A pilot trial of high-dose alpha-tocopherol
and ascorbate in early Parkinsons Disease, annals of
Neurology, 1992, 32 Suppl : S128 - 32
5) Fahn, S., The endogenous toxin hypothesis of the
etiology of Parkinsons Disease and a pilot trial of
high-dosage antioxidants in an attempt to slow the
progression of the illness, Annals of the NY Academy
of Science, 1989, 570 : 186-96
6) Ganong, W.F., Medical Physiology, Prentice - Hall
Int. Inc., 1993, 193
7) King, D., Playfer, J.F., Roberts, N.B.,
Concentrations of vitamins A, C & E in elderly patients
with Parkinsons Disease, Postgraduate Medical
Journal, Aug. 1992, 68 (802): 634-7
8) Kristensen, M.B. et al., L gemiddelkataloget,
Dansk Apotekerforening, MEFA & MEDIF, 1993, 317-
20
9) Rang, H.P, Dale, M.M., Pharmacology, Churchill
Livingstone, 698-703
10) Rascol, A., Montastrue, J.L., Rascol, O., Les
medicaments antiparkinsoniens, Rev-Prat, 1989 Mar.
9, 39(8) : 663-9
11) Stern, G., Lees, A., Parkinsons Sygdom, Dansk
Parkinsonforening, 1982
12) Tangeny, C.C., Tanner, C.M., Vitamine E and
PD,Neurology, Mar. 1993, 43( 3 pt 1): 634-5
13) Medlemsblade, Dansk Parkinsonforening, Juni &
Sept. 1994
14) Sandyk, R., Magnetic Fields in the therapy of
Parkinsonism, International Journal of Neuroscience,
Gordon & Breach Science Publishers, 1992 vol. 66
numbers 3-4, 209-35
15) The E-mail system,
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(Refs. 1, 2, 8, 11, and 13 are in Danish).
