AN ENGINEER’S APPROACH TO TREATING SYMPTOMS
OF PARKINSON’S DISEASE
BY SAMUEL D. MOORE
ABOUT THE AUTHOR
The author is an 84 year old, retired, electrical engineer, 36 years,
with 10 year’s experience of being treated for symptoms of
Parkinson’s Disease (PD). He is writing this on a $200 laptop
computer, with freeware tools and one finger on his left hand,
on a right handed person. He is a survivor of an explosion, that
killed 300 at London High School in New London,Texas on
March 17, 1937. He has also survived, type 2 diabetes and
prostate cancer.
He is married and has two daughters, with their significant others.
In addition, he has two grandchildren. He is the youngest of 6
children, two sisters and three brothers. They included, a
beautician, an executive secretary, a four star general, a senior
airline pilot (also a Mensa), and a geologist. Four of the 5 siblings,
also survived the school explosion. The beautician had already
graduated. Born in Mildred, Texas, he worked his way through
Kilgore Jr. College and Texas A&M, graduating with a BSEE.
He worked the summers, in the East Texas oilfield, as a roustabout.
WHY YOU SHOULD BELIEVE HIM
He was salutatorian, of his London High school graduating class,
1949, and won a scholarship, to Texas A&M, from the American
Petroleum Institute, for his top of the class, work at Kilgore Jr.
College. He has 9 hours graduate Work, in mathematics, from
Southern Methodist University. He has worked as an engineer,
senior engineer, senior nuclear engineer, test engineer, lead engineer,
project engineer, project manager and Neural Network applications
engineer. These jobs, were for the benefit of Goodyear Atomic
Corporation, General Dynamics, Texas Instruments and an
independent consulting company, in the special computer field
and in the application of neural networks to artificial elligence. He
holds five US and one UK patent. The subject of two of the patents,
resulted in a technical presentation at a seismic conference of The
American Petroleum Institute in Houston, Texas.
He was the lead engineer, for Texas Instruments, on a team testing
the first GPS receiver, at the Yuma Proving Ground, in 1977 and 1978.
THE HISTORY OF MY TREATMENT
FOR
SYMPTOMS OF PARKINSON’S DISEASE
I was diagnosed with PD, approximately, seven years ago. The diagnosing
neurologist, was a new graduate. She ran test after test, always advising
me that there was no cure. I decided that she was educating herself, at my
expense. I quit her and took a wait-and-see approach. A couple of years later,
the PD had advanced to the state of interference with my handwriting and
balance. At this stage, I resumed treatment to try and slow down the
progression of the disease. I attended group therapy for about a year, until
I lost a means of transportation. I had quit driving because of my slowed
response time.
My next neurologist had more experience with PD. He started off,
experimenting with Neupro, Requip, ropinirole, and SINEMET. We tried
several other drugs, but I cannot remember their names. In addition, I had
tried several, over the counter, treatments that I read about online. As I
found out later, SINEMET was the standard of treatment at the time, and
still is. We started out with one SINEMET tablet, three times a day. Then
we increased the dose, several times, with the goal of reaching two tablets,
three times a day. When we reached two tablets, the dyskinesia became
intolerable. It included, violent arm and leg movements, along with knashing
of teeth. The teeth knashing was so severe, that I feared I would
damage my teeth. We cut back to one and one half tablets and the dyskinesia
went away. This doctor referred me to a motion disorder specialist.
The new doctor, did a more thorough job of evaluating the progress of my
treatment for PD. He had a goal of my reaching three tablets, three times a day.
I became discouraged and attempted to wean myself off the SINEMET,
all together. This didn’t work. Instead of the symptoms lessoning, with the
reduced dose, they actually worsened. At this stage, I decided to trust the
doctor. We increased the dosage to two tablets and the dyskinesia lessoned,
to a tolerable level.
Due to a location change, I started with a new doctor. Then an insurance
change, resulted in, another doctor change. This fifth doctor, set a goal of
two tablets four times a day. I have been on this dosage, now, for
approximately two months. The dyskinesia continues at mostly a tolerable
level. It occurs at intervals throughout the day, mostly starting about one
hour after a dose and lasting thirty minutes to one hour. Lately, the dyskinesia
has started at bedtime and is more severe than I had been experiencing.
I discovered, by accident, that two menthol cough drops, calmed the dyskinesia.
I sometimes use this remedy, when dyskinesia is keeping me awake at night.
It is possible, that Menthol, the active ingredient in the cough drop, may be
used to alleviate dyskinesia during the treatment of PD.
LETS TALK ABOUT DYSKINESIA
Dyskinesia is not a symptom of PD, it is a symptom of the treatment for
PD. It exhibits itself with sporadic spasms of various parts of the body.
Tremors, are a symptom of PD, along with other symptoms. In my case,
the treatment with SINEMET, for PD has dyskinesia as a symptom.
PD is caused by a deficiency in dopamine available to a brain cell. The
deficiency is caused by a deficiency in levodopa. The deficiency in
levodopa is caused by a barrier’s resistance to the flow of levodopa.
The solution to the problem was to add more levodopa to the system.
The barrier is like the walls of a soaker hose. The higher the pressure
(level), the higher the flow rate. At a pressure that is high enough, there
is sufficient dopamine for the cell to function normally. If the pressure
falls, the dopamine level falls and the cell becomes unstable. The intensity
of the dyskinesia, is proportional to the level of levodopa. If the barrier’s
pore walls becomes rough, the levodopa will stick to the walls making the
barrier more resistant to the flow. A higher level of levodopa, will force
more levodopa across the barrier. Therefore, the dyskinesia’s intensity is
directly proportional to the highest level of levodopa, just before the level
begins to fall. Logically, one would expect the intensity to be proportional
to the level of levodopa at the time it triggered the incident. As the level of
levodopa increases, the higher flow rate, sweeps some of the stuck levodopa
off the walls of the barrier pore walls. At some level of flow, for some length
of time, the walls will be cleaned and the cell will exhibit normal flow. When
the levodopa source is removed, at the end of the treatment day, the walls will
clog again, and when the treatment resumes, the cycle will repeat itself. When
the volume of flow reaches a critical level, the dyskinesia will go away. A
lubricant would have the same effect as the high levodopa levels.
Based on the above, it appears effort should be made to find a cure for the
barrier’s pore walls rather than increase the levodopa. Or, as an alternative,
find a lubricant for the barrier’s pore walls.
SPONGE THEORY OF THE DOPAMINE PATHWAY
This theory is more probable, than the barrier in the dyskinesia discussion
above.
The filter is like a sponge. The sponge is designed, to soak up the desired
compound. This is accomplished, by giving the molecules of the sponge
the separation, to fit the molecule desired. This selected molecule, and
all smaller molecules, will readily be absorbed by the sponge. Adjacent
to the first sponge, is another sponge, configured to accept molecules, smaller
than the desired sponge. The smaller molecules, will then be syphoned, out
of the first sponge. This configured sponge combination, is bathed in veinous
blood. Since this configuration, is in contact with the blood, the smaller
molecules, will be drawn back into the bloodstream. This blood vein is made
of the sponge material combination, thus syphoning off the desired molecule.
This section of the blood vein, is called a capillary. The
permeability of the sponge, can be effected by absorption of another similar
molecule. In the case at hand, the desired molecule, is levodopa. The passed
molecule is dopamine.
See Figure 1, for a pictorial of the Dopamine Pathway. The levodopa sponge
(orange), soaks up the levodopa from the arterial bloodstream. The levodopa
sponge, gives up the levodopa to the dopamine factory. Excess levodopa, is
passed on to the veinous blood stream. The dopamine factory, breaks down
the levodopa, dividing it into levodopa and some unknown compound.
The dopamine is soaked up by the dopamine sponge, and passed on to the
brain cell(purple).The brain cell uses the dopamine as fuel to produce neural
pulses, as required by the other parts of the brain. The left over dopamine,
and the waste product from the brain cell, are passed on to the veinous
bloodstream.
The system, also, serves as a drain to keep puddles, of one of the compounds in
the system from building up. If one compound, is over produced in a capillary,
the excess, will spill over the drain, thus, relieving the back pressure.
SEARCH FOR FACTS
l There are an infinite number of variables, effecting the solution.
l SINEMET is a four to one mixture of levodopa and carbodopa.
The standard tablet, contains 100 mg of levodopa and 25 mg of
carbodopa. The carbodopa is for the purpose of alleviating the
adverse side effects of levodopa.
l Levodopa is a precursor to dopamine.
l Dopamine is manufactured from levodopa in the brain, and is
used to complete the path, triggering the brain impulses. In order to
function, it must pass through a barrier. Lack of levodopa, resistance
by the barrier and/or damaged receptors can cause erratic functioning,
of the brain.
l Increasing levodopa, is a way of insuring the supply of dopamine.
l PD is caused by a resistant barrier and/or a clogged receptor. In
either case increasing, the availability of levodopa should help.
Correcting the barrier permeability or correcting the receptor problem
would be desirable.
l Increasing the level of levodopa, is possible, but, not without side
effects.
l SINEMET absorption time is approximately one and one half hours.
l SINEMET half life is approximately three hours.
l SINEMET CR absorption time is approximately one and one half
hours.
l SINEMET CR half life is approximately five and one half hours.
l An automatic pump, for delivering SINEMET, is technically feasible,
but, too expensive and with questionable reliability.
l Menthol has been used in test safely, at strength up to 100 mg and in
food up to 20 mg.
l Menthol has a half life, of approximately, one hour.
ASSUMPTIONS USED IN THE ANALYSIS
l Straight lines can be used in the graph to replace the logarithmic lines,
l Limits on dose level and time of treatment are ignored. This is a teaching
tool.
l Plot the SINEMET level, in the system, versus the time, after the first
dose of the day.
l Analyze the plots against the known side effects of the treatment profile
and observe the effect of the treatment, on my symptoms.
l Make conclusions from the analysis and other research data.
DATA ANALYSIS
FIGURE 2 ANALYSIS
Figure 2, shows the last two profiles my doctors prescribed. The green
profile is my current profile. This profile provides 200 mgs. more levodopa
than the purple profile. It also has shallower valleys in the level, making it
less susceptible to dyskinesia. The shallower valleys are the result of the
shorter time between doses.
I have observed that my dyskinesia is less severe with the 4 dose profile
than with the three dose profile. This correlates with the shallower valleys
with the shorter time between doses. I also have noticed that when I fail to
take a dose I have more severe symptoms. It is harder for me to take doses
on time with the shorter time between doses.
FIGURE 3 ANALYSIS
Figure 3, shows the effect of the half-life characteristic of the elimination of
levodopa from the bloodstream. The doses used in the graphs exceed the
maximum doses that I have seen recommended. The dose levels used are to
demonstrate the effect and should not be considered a recommendation.
The profile in green is my current profile. The half-life effect, is to cause the
graphs to get closer together until they blend.
FIGURE 4 ANALYSIS
Figure 4, shows how the dose profile can be shaped by tapering the doses.
In this figure, the first dose is 4 tablets, the second dose is three tablets,
the third dose is two tablets and the fourth dose is one tablet. The result
is a quick rise to a therapeudic level. The valleys are shallow, limiting
the dyskinesia.
CONCLUSIONS
The conclusions reached here, are from the analysis, discussed
above, along with my own observations of the way my symptoms
were modified by the various treatment schedules that I have
Experienced.
l All people are different, so the treatment needs to
be individualized.
l One size does not fit all.
l Make the doctors work for their pay. Trust your doctor, but
make them work hard.
l Don’t be afraid of the word “WHY”.
l Start treatment early. It is easier and more effective.
l Don’t take a wait-and-see attitude.
l A graph is worth it’s weight in precious metal, when planning
your treatment profile.
l Consider all your options, ie: SINEMET, SINEMET CR, 100/25,
200/50, pump.
l The PD is still incurable, but it can be slowed.
l Your treatment schedule, can be adjusted, to give effective
treatment, and minimize, the side effects.
l Each person must be aware of symptom changes and discuss
them with your doctor, he is still working for your good.
l SINEMET is still, for the time being, the best drug in the fight
against PD.
l The absorption time, plus twice the half life time, should be greater
than, the period between doses. This allows build up of the levodopa,
for effective treatment.
l Menthol may be a treatment for dyskinesia. More test are needed.
l Exercise is a great tool.
l The ideal profile, for me, is two tablets, taken four times a day.
This profile gives the minimum, peak dose, while delivering the
maximum, total dose. The minimum , peak dose, minimizes the
dyskinesia. The maximum, total dose, minimizes the symptoms
of PD. I started, the profile of 1 tablet, taken five times a day.
Within 2 days I knew it wasn’t working. I immediately returned to
“my” profile.
l The symptoms of PD and dyskinesia overlap, such that, as the
levodopa increases, the symptoms of PD decrease, and the symptoms
of dyskonesia increase. The patient see’s a threshold, above which,
the dyskonesia intensifys.
Below this apparent threshold the two symptoms appear to cancel
one another out. As the level of levodopa decreases, the symptoms
of dyskinesia decreases, and the symptoms of PD increases. The
patient see’s a threshold below which the symptoms of PD increase.
Inversely, as the level of levodopa decreases the dyskinesia symptoms
decrease, and the symptoms of PD increase. The patient see’s a
threshold below which the PD intensifies.
I will try to update this section, as I think, and hear, of helpful
information, so keep tuned in. I welcome your comments, good
and bad. I may, or may not, respond. I am writing this, to be
helpful to all, scientist, doctors, and patients. I realize that I am
an engineer, this subject was not a part of my education and
experience. I saw a need, and am attempting to fill it.
