The following is a close to verbatim transcript of the March 7th Satellite
Symposium Question and Answer portion of the program.
 
Dr. Dee Silver, from San Diego, California, moderated the question and
answer period.
 
Q. What can a Parkinson's patient do to sleep better at night?
 
D Silver: I think that there are a combination of things that are helpful.
   1. Have plenty of exercise and activities during the day.
   2. Don't take lots of naps during the day.
   3. Don't take Eldepryl after Noon or 1 p.m.
   4. Sleep in a quiet place, free of noises
   5. Use some of the tricyclates or anti-histamines
       Benedryl low dose at bedtime
       Elavil
 
If you have nocturnal symptomology, meaning tremor or rigidity,
that wakes you up at night, it is important to consider how to
change your medication. Tailor your individual treatment. If you
have urinary problems, that require you to be up many times
during the night, consult with your doctor about the possibility
of the cause being a Neurogenic bladder and its treatment which
can be complex but helpful.
 
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A document discussing Neurogenic bladder and its treatment is
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//DBlook   JOB   Echo=No
Database Search DD=Rules
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print all 4349
 
 
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Fort Myers Florida
 
Q. Do Parkinson's disease patients ever regain their loss of
   brain cells or is this the very best day of their lives?
 
Dr. Tatton: Well, they don't recover brain cells if they have
died but it is not necessarily the best day of their lives.
 
People like Galen Finch and other people, and we are beginning
to think this way as well. The death process is probably a
prolonged process, in which the cells are first damaged and the
'end of the road' is likely to be the apoptosis process, as I
talked about. In between, some proportion of the cells become
dysfunctional so when you gave the numbers of 20 to 40 percent,
before we started to see the disease, maybe there are 5 to 10
percent of the cells that are not dead but dysfunctional. We have
an opportunity to recover or get back those cells so that you may
have a better day.
 
 
 
Grand Rapids, Minnesota
 
Q. Some recent reports, suggest selegiline's (Eldepryl, deprenyl)
   benefit may not last for a number of years.
 
Dr. Olanow: It's a very difficult question to answer, because, in
order to determine if selegiline benefit lasts for years, you would
have to have controlled groups that were follow for that length of
time and compare them with what is happening to them with their
Parkinson's.
 
One of the things that we know is that selegiline does not stop
the progression of Parkinson's disease, the question is whether
it slows it down. To my mind, the study that most closely looks
at that from a specific point of view is that which I described
for you earlier and that only looks out about 14 or 16 months. I
think that for now that there is just not information to say
what happens several years down the road.
 
Tucson, Arizona
 
Q. Does Deep Brain Stimulation (DBS) produce the same results
   clinical that the ablative surgical procedures?
 
Dr. Kordower: In terms of the Stimulation of the VIM of the
thalamus, the constellation of symptoms that are improved are
different than pallidotomy or transplantation. Tremor control
is effective when the VIM of the thalamus is stimulated. There
may be other brain regions that may be sensitive to deep brain
stimulation such as the globus pallidus, or the subthalmic
nucleus and remains to be determined if these nuclei which are
much more located in the direct main circuitry of the basal
ganglia. Stimulation in these regions may give a more widespread
and efficacious relief to more parkinsonian symptoms.
 
Ridgecrest, California
 
Q. What new medications are on the horizon and can you group
   them into specific types, giving the names if possible?
 
Dr. Olanow: There are fortunately a lot of new medications that
are being evaluated. Some are in the process of being assessed
by the FDA, for the use in the treatment of Parkinson's disease.
 
Dopamine Agonists
 
Ropinerole
Pramipexole
 
These dopamine agonists are potent, D2 receptor stimulants, in
some ways similar with Pergolide (bromocriptine). They are being
tested predominately in early stage disease to see if they can
be used to delay the start of levodopa, and also to see if they
could reduce the likelihood of adverse effects.
 
Cabergoline
 
A long lasting, one dose a day agonist.
 
Apomorphine
 
A drug used in Europe for advanced patients in which freezing
is a problem. May be injected and used as a rescue drug for
those who freeze in the middle of a crosswalk on a busy street.
It is also valuable in a post operative setting in which patients
may not be able to swallow.
 
COMT Inhibitors
 
COMT inhibitors prolong the effective dose period and in some
cases will turn "On" those patients whose levodopa dosage is not
enough.
 
Fort Myers, Florida
 
Q. Is melatonin of any benefit, or could it have side-effects?
 
Dr. Tatton: Melatonin is an agent that resets part of the brain
that controls our sleep and awake cycles. It's been an experimental
agent for some time. I don't think that there have been wide-spread
trials in relation to Parkinson's disease benefit.
 
Cape Coral, Florida
 
Q. When do you begin Sinemet treatment and when is more dosage, too much?
 
Dr. Silver: I use Sinemet CR in the younger and Sinemet regular
in the older patient when functional impairment occurs. When
Activities of Daily Living (ADL) are significantly affected.
 
Without question, levodopa (Sinemet) is the biggest, most
powerful drug we have for the treatment of parkinsonism, today.
 
How much is too much? Too much is always determined by monitoring
side effects/benefits.
 
 
Q. If Parkinson's disease is genetic, is there any evidence that
   it is only passed down to one gender?
 
Dr. Olanow: At the present time there is some evidence that at least
in some families, Parkinson's disease is genetically transmitted,
but they are few and far between. Probably only 5% of cases follow
an autosomal dominate pattern. That doesn't mean that the other
cases don't have a genetic component, but what is likely a genetic
component that is brought into play by circumstances that involve
another form of stress, such as exposure to a toxin. For example
if you were born with the inability to metabolize a particular
toxin, if you don't get exposed to that toxin, then you don't get
the disease. On the other hand, if you don't have the defect, and
you are exposed to the toxin, you don't get the disease. What you
need is what was referred to previously, you need a "Double Hit",
you need to have the defect and also be exposed to the toxin.
That's becoming a very popular theory.
 
With respect to cases where there is proven Autosomal Dominate
inheritance, there is no evidence because it is autosomal rather
than X-linked, that it specifically affects one sex member more
than the other. With respect to the other, it is not yet proven
what role genetics plays, only interests in the possibility that
it contributes to risk nothing to suggest more that one sex,
however it is noteworthy to note that Parkinson's disease seems
to effect males more.
 
Alberta, Canada
 
Q. How is dopamine production, in the brain, measured in humans
   and animals?
 
Dr. Tatton:  There are a number of ways in doing that. One can do
it indirectly by looking in the cerebrospinal fluid, in humans,
and looking at the break-down products of dopamine and getting
some idea of the dopamine productions. This is not a great way
of doing it. In animals, or with post-mortem brain tissue, one
can literally remove specific areas of the brain and measure
dopamine and its break-down products with techniques like hplc
and other techniques. Look at enzymes or proteins directly with
ink stains or aminocytochemistry. Lastly you can get some ideas
of dopamine by using PET scans.
 
San Diego
 
Q. How can you tell if you are over-medicated?
 
Dr. Silver: There are a number of ways to determine if you are
over-medicated and to understand that concept of over-medication,
we have to think about the toxic features that we see. The ones
that I am more concerned about are the involuntary movement
disorders, the dyskinesias. Peak dyskinesias are those that
occur between doses. That usually means toxicity. Another important
area, is the neuropsychiatric manifestations that occur, especially
those who have memory difficulty.
 
Side-effects that are early warning signs of over-medication are:
 
Early personality changes
Nightmares
Hallucinations
Confusion
Disorientation
Delusions
 
Now we have clozapine (Clozaril) that is of significant benefit.
 
 
Waco, Texas
 
Q. Is there evidence of a specific toxin, such as MSG or some
   other toxin, that is present in the environment today
   that causes Parkinson's disease?
 
Dr. Olanow: About 10 years ago when Bill Langston and his
colleagues identified MPTP injections as associated with
Parkinson's, there was considerable interest in the possibility
that there were MPTP-like toxins in the environment.
 
Outside of MPTP there have been no toxins identified that
produce Parkinson's syndrome. There are several toxins that
can produce parkinsonian feature and have some aspects that
resemble Parkinson's disease, such as manganese, carbon monoxide,
carbon disulfide, but these are indeed different and probably
not the same. There are a number of toxins that are being
investigated, which could eventually have effects on dopamine,
but as yet none of them have been directly linked to Parkinson's
disease or Parkinson's disease-like syndrome other than MPTP itself.
 
Q. Is pallidotomy a routine procedure and who should be selected
   to do that procedure?
 
Dr. Olanow: I think that this is an important question and I
think that it is an appropriate question in a forum like this.
I think that there are many opinions what I'm going to say should
be taken in context that I am just giving you my own personal opinion.
 
Pallidotomy is a procedure that has been done since 1940 or
since 1950, so that a lot of people have done pallidotomy. There
have been claims of benefit from pallidotomy dating back to that
time. The big advance came in the 70s or 80s when Laitenen,
using the Leiksell technique, reported that if you did the
pallidotomy in a slightly different location, which was called
posteroventral, the quality of the results were improved.
Pallidotomy is also done targeting something lying between the
internal capsule and the optic region so it is possible during
the lesioning, damage could be done to the optic region.
Therefore, one has to take into consideration the improvement
versus the adversity that could pursue. What has really triggered
the resurgence of pallidotomy aside from improvements in
stereotactic technique and MRImagery, is increased insight into
the organization of the basal ganglia which provides a scientific
reason why a lesion in this area might be expected to be helpful.
Refined techniques, like microelectrode recordings permit very
precise detection where exactly you are. I tell you all of this
because the pallidotomy that is being done today in the highly
academic centers is not the same being done routinely in
neurosurgical operations in non-academic environments. There are
many questions that remain to be answered like what is the best
site for the lesion, is microelectrode technology essential to
get the best results, how long do the improvements last, what are
the side-effects, who are the very best patients for the
pallidotomy. I think that these kinds of questions need to be
answered. You must look at that in the context that there are
very encouraging reports, particularly with dyskinesia that suggest
that pallidotomy is a wonderful procedure and very beneficial for
the appropriate patient. Taking all of that together, I would
encourage one to think of pallidotomy as a procedure that still
should be performed by those skilled in stereotactic surgery,
expertise in neurology and expertise in neurophysiology, with
expertise in clinical trials. In an effort to come to a conclusion
that answers these questions in the best possible way, so that we
can offer this procedure in the most effective way to our largest
possible population. I personally don't think that we have reached
the point where all pallidotomies can be considered the same and
that just anyone should be doing the pallidotomy without concern
for assertainment, full reporting of results, and full investigation
of associated factors that might influence results.
 
 
Houston, Texas & Alberta, Canada
 
Q. What is the best times to take your medicines and do meals
   have any effect on Sinemet, Eldepryl and a dopamine agonist?
 
Dr. Silver: Eldepryl, take in the morning and around noontime.
Meals by and large do not effect the absorption of Eldepryl. Sinemet
on the otherhand, can be blocked by the large proteins. Not only
does the amino acids block the absorption in the stomach but the
transport of the levodopa across the blood-brain barrier is
affected. The other important concept is that dopamine agonists,
are not affected by meals.
 
Q. Would you please explain again what a free-radical is and the
   aspect of anti-oxidants in vitamin E?
 
Dr. Tatton: Atoms that are stable have two electrons in orbit
around them. Unstable atoms have one electron in their orbit. These
unstable atoms are called free-radicals. If the free-radical is
able to 'steal' an electron from a stable electron, it is called
oxidation. Atoms that have an even number of electrons in their
orbit and have the ability to change or absorb those atoms with
only one, are called anti-oxidants. Vitamin E is such an
anti-oxidant. As Dr. Olanow, it was used in the DATATOP study
compared with deprenyl. In that study, it was shown to have no
benefits in terms of the Parkinson's patients studied.
 
Savannah, Georgia
 
Q. Could you tell us what a Lewy body is, what is its significance
   and what role does it play in Parkinson's disease?
 
Dr. Kordower: It is the defining feature of Parkinson's disease.
Inside the cell there is an occlusion which histologically is seen
preferentially and also exclusively with patients with Parkinson's
disease. It is found in regions know to degenerate, such as the
substantia nigra and the locus cerolious and again it is used as
the hallmark histological diagnostic feature of Parkinson's disease.
 
San Diego, California
 
Q. Please explain a reason for freezing that occurs suddenly and
   unpredictably.
 
Dr. Olanow: That is one of the troublesome features of Parkinson's
disease, especially as they advance. Some can have freezing while
in the 'On' stage, that is while they are responding to levodopa.
Some can have freezing during the 'Off' stage, that is the period
after the dose has lost its effectiveness. Characteristically, it
occurs suddenly. The patients stop in the middle of a movement, and
when they are changing from one environment to another like they are
walking through a doorway. They stand for seconds or minutes at a
time before they are able to restore function. It is different than
the 'On' or 'Off' response that we talk about relative to levodopa.
It does not respond relatively well to levodopa. For the most part,
we do not have an effective treatment for it and do not fully
understand it pathophysiology.
 
Tacoma, Washington
 
Q. Do nutritional supplements combat free-radicals and can they
interfere with the aspects of Parkinson's disease?
 
Dr. Tatton: Clearly, it is an attractive idea that dietary changes
can reduce the destruction of free-radicals. The jury is still out
on this. There are a number of supplements that are out, that claim
to do this. There haven't been any studies that support the idea that
simple dietary supplements will reduce free-radicals in the brain,
especially the parts of the brain effected by Parkinson's disease.
 
Fort Myers, Florida
 
Q. Give me a simple treatment format for orthostatic hypotension.
 
Dr. Olanow: Orthostatic Hypotension refers to a drop in blood
pressure upon standing. This can be mild and innocent found on
blood pressure taking as one changes from lying to standing
positions, but it can also be extremely troublesome and be
associated with syncope episodes (light-headedness, fainting)
and literally prevent a patient from rising to their feet and
being able to walk, so it can be very disabling. It usually
results in autonomic dysfunction in parkinsonian patients. It is
not rare to occur in Parkinson's disease, but is usually very
mild. If it is present to a severe degree, it suggests that it is
not Parkinson's disease but rather a more wide spread degenerative
disease called, Multiple System Atrophy (MSA) in which autonomic
involvement is prominent. When patients have autonomic dysfunction,
there are a few things that can be done to treat them
symptomatically. One thing is to increase their salt intake always
bearing in mind that that may have an adverse effect on blood
pressure. Patients can also take a drug called Fluorinef which is
a form of steroid that retains salt and control blood pressure.
0.1 to 0.2 mg/day is usually sufficient. If you need more than that
it is not particularly helpful. In the most severe cases, one could
wear stockings which are like an antigravity stocking that wraps
up all the way to your waist. If you wear stockings only to the
thigh, it is not particularly helpful. They have to be worn to the
waist to be effective. In regions like Florida where it is hot and
humid, you can imagine that this is not a particularly popular
therapy. Patients in this environment, even though they need them,
will not take them.
 
Dr. Silver: When I do not see a patient who has orthostatic
hypotension for a while, I check their medicines that their HMOs
may have prescribed since I saw them last. I especially look for
anti-hypertensives and see if we can adjust their dosage.
 
 
Charleston, West Virginia
 
Q. With regards to recent reports, smokers have a lower
   prevalence of Parkinson's disease. Can you shed any light
   on why that may be so? Is there any protection from being a smoker?
 
Dr. Tatton: There have been an number of reasons suggested for this.
People who smoke have fairly high levels of carbon monoxide in
their blood. Carbon monoxide can serve as an antioxidant and can
reduce free-radical damage. It is like taking one poison to benefit,
another.
 
Dr. Olanow: People with Parkinson's disease were compared to
non-smokers. People who smoke are risk takers. It has also
been suggested that people who smoke, may not live long enough
to get Parkinson's disease.....:)
 
Florida
 
Q. Could you please shed some light on the concepts in trophic
   factors and in transplantation, please?
 
Dr. Kordower: There are a number of ways that trophic factors
and transplants work independently and together. I showed you
that over 200 thousand cells survived in our transplant patient
but in truth, that was only 6 to 7% of the ones we put in. There
are a number of studies in the laboratory by my group and other
groups demonstrating that substances called trophic factors. A
trophic factor is defined as a substance which supports the
viability or survival of a cell and which we can use to get
larger numbers of cells to survive in the animal model of
transplantation. That is one way that a trophic factor can
help transplantation. The other very interesting area of research
is to use the trophic factor to prevent the degeneration of the
nigral neurons, much in the same way Drs. Olanow and Tatton have
been describing anti-oxidants to try to prevent the degeneration
of nigral neurons. Probably the most promising of the group is a
trophic factor called a Glial Derived Neurotrophic Factor (GDNF).
Some pioneering work, here in Denver by Dr. Barry Hopper and his
colleagues have demonstrated that you can inject in GDNF and
prevent the degeneration of nigral cell neurons in animal models
of Parkinson's disease. What makes this trophic factor particularly
exciting, relative to others is the lasting effect. A single
injections of GDNF can last for weeks or months. Based on the
success of recent work on animals and primates, a number of
centers including Dr. Lang at the University of Toronto and
our group headed by Dr. Goetz at Rush-Presbyterian Medical
Center, will be soon be initiating a clinical trial as to whether
the inter-cerebral administration GDNF will be able to slow the
progression of Parkinson's disease and potentially have a
symptomatic effect on the signs and symptoms of this disease.
 
Dr. Tatton: It is probably worth mentioning one other aspect of
trophic factor. Years ago to get them, they had to be extracted
from brain tissue. It was very expensive and the yield was only
very small amounts. Recombiant-DNA methods now allow making the
trophic factors very simply. This is a big factor in the
possibility that these may be effective therapeutic tools.
 
 
Florida
 
Q. Are dopamine agonists an effective treatment by themselves or
   do they always have to be in combination with Sinemet?
 
Dr. Silver: Dopamine agonists can be used in the concept of
'dopamine sparing' strategies. In early Parkinson's, Eldepryl
and then an agonist may be used...keeping a close eye on the
motor functions and then later adding Sinemet.
 
 
Oxford, Ohio
 
Q. For many parkinsonians who experience cognitive and memory
   problems, is there any drug that can be of benefit?
 
Dr. Olanow: In the older parkinsonian, this is common. It has been
estimated that 1/3 will develop a dementia at some stage. At
pathology, approximately 50% of Parkinson's disease patients have
changes in their brain consistent with Alzheimer's disease change.
One of the arguments suggesting at least an overlap between these
two conditions. In addition, Parkinson's patients also get Lewy
bodies in their cortex giving rise to a syndrome called Lewy body
dementia. This can be a very troublesome problem to deal with and
to be quite candid, if we are dealing with dementia per se,
difficulty with confusion, thinking and memory there are very few
things one can do. One of the things you could do is make sure that
the patient is not taking other drugs which interfere with mental
function. Another thing is to make sure that the patient is not
taking other anti-parkinson drugs that aren't particularly effective
but have mental side-effects like artane or Symmetrel(amantadine).
Thirdly, one could consider reducing the amount of levodopa necessary
to control the Parkinson's disease.
 
If the patient has hallucinations, not dementia, One can look at
clozapine, the atypical neuroleptic or ECT. These drugs may control
hallucinations and at the same time allow the increase of Sinemet
to better control the Parkinson's symptoms.
John Cottingham    "The parkinsn list brings Knowledge, Comfort, Hope, and
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