Key Topics in Brain Research
Early Diagnosis and Preventative Therapy in Parkinson Disease
An Orange Volume published by Springer-Verlag,  Wein, New York 1988
 
Table of Contents
 
1. The premorbid personality of patients with PD
2. PD the development of dimentia and ageing
3. Psychometric signs of early dimentia with special consdiereation to PD
4. Autonomic nerverous system screening in patients with early PD  pg41
5. Clinical and biochemical characteristic of early depresion in PD  pg49
6. Psychomotor investigation in depressed patients by comparison with PD
   patients.
7. Long term measurement of tremor early diagnostic possiblitites.
8. Tremor in electrically illicited long latency reflex in early stages of PD
9. Positron Emmision Tomogrohy in PD glucose metabolism.
10. PD studied with PET scanner
11. Dopimergic Neurotransmission and status of brain Iron
12. Diagostic relevence of Lewy bodies and other inclusion in PD
13. Cytosketal pathology of Lewy bodies.
14. Catecholime in blood and CereboSpinal Fluid
15. Platelet and MOA-B activity in humans and stumptail monkeys
16. Invivo effects reversible in MOA-B inhibitor RO-19-6327
17. Aspertate, Glutimate and Glutimine in the platelettes of PD patients
18. Hypothalamic disfunction in neuro indoctrine research in PD
19. Histo chemistry of MOA subtypes in the brain stem of humans in relation
    to the Radical hypothesis to PD
20. Transplantation of dopamine synthesisizing cells in PD therapy
21. Iron therapy in PD
22. Stimulation of endogenous presynaptic L-dopa biosynthesis by the iron
    compound Oxyferriscorbone
23. Provisional experiences with the combinationm of L-dopa and L-deprenyl.
24. Dopamine Agonist treatment in early PD
25. Subcutaceus Apomorphine in PD
 
Random Quotations:
 
The early diagnosis of extra pyramidal disease seem in the first place to be of
particular value in genetically determined diseases. The early diagnosis of PD
presents a much more difficult problem. If we start with the fact that the
disease manifests itself subclinically for years before clinical symptoms
appear.  It should be possible to recognize it by a carefully directed early
methodology.
 
Various studies indicated that the premorbid personality of PD  patients is
characterised by depression, introversion, rigidity and inflexibility. These
findings are confirmed by twin studies in which it became evident that the twin
that developed PD was less extroverted, more introverted and more depressive
than the un-affected twin.
 
Patients with PD complain very early on of subjective and autonomic
disturbances which tend to be ignored because they are overshadowed by the
promanent motor disturbances.  These subjective symptoms generally  take the
form of deafness, parathensis (crawling of the skin) and ache and pains.  In PD
perhaps we ought to consider the possibility that video recordings might help
us early on to document deviations from the patient's normal state.  One of the
things one notices is that stress or emotional tension can provoke tremor in PD
patients. It might be worthwhile to use a stress inducing substance prematurely
to elicit resting tremor or by administering short acting dopamine agonist
perhaps to discover some threshold dose to which a healthy person would not
show any movement but that in a PD patient would respond by showing akinesia
and rigidity.  Because it is the complex motor performance that is affected in
PD, it should be possible by refining the testing procedures to detect motor
disturbances earlier that is currently possible.
 
PD has become a paradymne of the way patho genenisis therapy of a neurological
diseases can be investigated.  With remarkable consistancy patients with
various personalities are dominated by traits of moral rigidity, inflexibility
combinded with a tendency toward depression and introversion.  Many of the
early authors have taken a psychodynamics view of their findings and have
postulated causual role of lifelong suppression of aggressive tendencies and
emotional deprivation leading to the eventual development of PD.   Some
patients appear to be over controlled in their premorbid personalities  which
in this test is defined by features as "talented in dealing with money", over
orderliness, over ambitious, timid, over self reflective, swallowing anger, and
dependent.
 
Geissen test was selected as the personality inventory for this investigation
because it provides both self and outside assessment of the patients
personality features.   So that the bias of retrospective judgement could be
kept as low as possible.  PD patients are generally industrious with a
moralistic attitude to life.  Chronic interpersonal conflict has been remarked
as the suppression of agressiveness.  The typical PD patient has been making a
religion of success by constantly striving for independence from outside
interference and seeking freedom from authority, albeit within a framework of
social conformity.  The personality is hidden behind a social mask where we
find strong hostile and sadistic impulses, excessive degree of self control,
suppressing emotional and instinctual drives.  A compulsive neurotic character
with lack of self assertiveness finds expression in being industrious, exact,
and with great ambition.  Their mental welfare was dependent on job
achievement.  These behavior patterns were laid down in early childhood around
age 2 years when effective life was profoundly influencing  the motor system.
Here, lack of self assertiveness was regarded as central to the PD patient.
These individuals had a permanent readiness for motor activation but inhibition
lead to motor blocking and ambivalence. Psychological methods to assess  such
personality is the Geissen psychometric personlity inventory.  The
neurophysiological mechanism underlying the rigidity still evades explanation.
 Tremor is usually recorded by accelerometers.  Most of the energy is
concentrated around a narrow spectrum of 4 Hertz.
 
The "Stroop Task" consists of a matrix words of common colors, red, blue, etc.
Each word was printed in colored ink, but the color did not correspond to the
word color.  For example, the word RED might be printed in blue ink.
 
To date an early diagnosis of PD is not possible with neurophysiological
methods.  Selective degeneration of dopamine containing neurons in the compact
zone of the substantia nigra are resultant reduction of the dopamiergic
enervation of the striatial nuclei represent the major pathological process of
PD.
 
Energy requirments of the  brain is almost exclusively supplied by glucose and
it metabolism. Currently, there is no PET study diagnosing patient in the early
phases of the disease or even in preclinical stages has been performed yet.
 
A highly characteristic uneven distribution of iron in the human brain,
suggests a functional importance of this metal.  Only until recently little
attention was paid to brain iron, the most abundant metal in the body and in
the earth's crust. The highest concentrations were found in the globus pallidus
and the substantia nigra. The increase of iron and ferrentus in the substantia
nigra of Parkinsonians, the inability of iron to cross the blood brain barrier,
unaltered dopamine D2 receptors in the PD brain, must be reconciled with
studies of BirkMeyer who reported significant decrease of disability score
parkinsonism response to iron complex therapy.
 
The results point out that platelette asperatate, glutimate and glutimine are
significantly decreased in PD patients.   There is a correlation between the
severity of PD and the degree of decrease in the investigated amino compounds.
 The described changes of aspertate, glutimate and glutimine in PD patients are
unexplained.
 
Two actual theories try to explain the biochemical mechanisms, formation of
cytotoxics superoxide radicals and blocking of energy metabolism. It has been
suggested that free radicals which have their origin in the auto oxidation of
dopamine plays an important role in the eitiology of idiopathic PD.
 
The positive effect of low protein diet on efficacy of Levo-dopa was first
observed many years ago.  A diet with restricted protein intake during daytime
with a balancing nighttime intake was followed by a reduction of PD disability
and fluctuations.  The iron compound oxyferriscorbone has been used been used
as a novel medication.  In 66% of the patient treated showed benefits.  22%
showed very good improvment, 44% showed moderate improvement.
 
The theraputic application of alphamethyltryosine the inhibitor of tryosine
hydroxylase deteriated the disability of PD patients indicating that this
enyzme plays a key role in this disease.
 
On the basis of these findings we started to treat PD patients with iron.  The
crucial feature of our approach was to use oxyferriscorbone which is very
special compound inwhich iron is tightly bound to ascorbic acid in its Fe2 Fe3
form.  According to these studies there is no doubt the clincial benefit of
oxyferriscorbone in PD patients.  It should be added that of the other
available iron drugs in the European market , oxyferriscorbone was the only one
exhibiting beneficial effects.