Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.

https://jnnp.bmj.com/content/jnnp/55/3/181.full.pdf

Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

Parkinson's disease: Mechanisms and models

The Lewy body is a distinctive neuronal inclusion that is always found in the substantia nigra and other specific brain regions in Parkinson's disease. It is mainly composed of structurally altered neurofilament, and occurs wherever there is excessive loss of neurons. It occurs in some elderly individuals and rarely in other degenerative diseases of the central nervous system. In 273 brains of patients dying from disorders other than Parkinson's disease, the age-specific prevalence of Lewy bodies increased from 3.8% to 12.8% between the sixth and ninth decades. Associated pathological findings suggest that these cases of incidental Lewy body disease are presymptomatic cases of Parkinson's disease, and confirm the importance of age (time) in the evolution of the disease. In view of the common and widespread occurrence of this disorder we propose that endogenous mechanisms operating in early life may be more important than environmental agents in the pathogenesis of Lewy bodies and Parkinson's disease.

https://jnnp.bmj.com/content/jnnp/51/6/745.full.pdf

The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.

Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations.

We develop a theoretical framework that shows how mesencephalic dopamine systems could distribute to their targets a signal that represents information about future expectations. In particular, we show how activity in the cerebral cortex can make predictions about future receipt of reward and how fluctuations in the activity levels of neurons in diffuse dopamine systems above and below baseline levels would represent errors in these predictions that are delivered to cortical and subcortical targets. We present a model for how such errors could be constructed in a real brain that is consistent with physiological results for a subset of dopaminergic neurons located in the ventral tegmental area and surrounding dopaminergic neurons. The theory also makes testable predictions about human choice behavior on a simple decision-making task. Furthermore, we show that, through a simple influence on synaptic plasticity, fluctuations in dopamine release can act to change the predictions in an appropriate manner.

https://www.jneurosci.org/content/jneuro/16/5/1936.full.pdf

A framework for mesencephalic dopamine systems based on predictive Hebbian learning

1. Es wurde die Verteilung des 5-Hydroxytryptamins (5-HT) im normalen Gehirn des Menschen untersucht. In den 5-HT-reichen Regionen nahm die Konzentration dieses Amins in der folgenden Reihenfolge ab: Formatio reticularis — Substantia nigra — zentrales Hohlengrau des Mittelhirnes — Nucleus caudatus — Putamen — Hypothalamus — Thalmus — Pallidum.

[Distribution of 5-hydroxytryptamine (serotonin) in the human brain and its behavior in patients with Parkinson's syndrome].

1. Die fruheren Befunde uber eine Abnahme des Noradrenalins im Hypothalamus und des Dopamingehaltes im Neostriatum parkinsonkranker Patienten wurden an sechs weiteren Fallen bestatigt. 2. Gehirne von parkinsonkranken Patienten (drei Falle), die uber langere Zeit ante exitum verschiedene MAO-Hemmer erhielten, wurden auf ihren Noradrenalin-, 5-Hydroxytryptamin- und Dopamingehalt untersucht. 3. Die Untersuchung ergab, das der Noradrenalin-und 5-Hydroxytryptamin-Gehalt durch die MAO-Hemmer-Therapie normalisiert bzw. sogar betrachtlich uber die Norm gesteigert wurde. Der Dopamingehalt des Neostriatums wurde durch die MAO-Hemmer-Therapie dagegen nicht wesentlich beeinflust. 4. Aus diesem Verhalten wird auf einen prinzipiellen Unterschied in der Stoffwechselstorung, die der Abnahme des Dopamins bzw. des Noradrenalins und 5-Hydroxytryptamins zugrunde liegt, geschlossen. 5. Die erhobenen biochemischen Befunde, die auf eine Storung der Speicherungsmechanismen fur die Gehirnamine zuruckgefuhrt werden konnten, und die klinische Wirkung der MAO-Hemmer auf die Parkinson-Symptomatik werden verglichen und kurz diskutiert.

Birkmayer W

Papers

Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations.

[Distribution of 5-hydroxytryptamine (serotonin) in the human brain and its behavior in patients with Parkinson's syndrome].

Zur Biochemie des Parkinson-Syndroms des Menschen

[Homovanillic acid in the cerebrospinal fluid: studies in Parkinson's syndrome and other diseases of the CNS].

Behavior of monoamine oxidase in the brain of man after therapy with monoamine oxidase inhibitors