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.