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 ascending monoamine pathways in the rat brain are demonstrated by the pile up of fluorescent material occurring in the axons after various types of lesions. The anatomy of the pathways is outlined in drawings of frontal sections of the brain and the origin and termination of several pathways is determined by studying the anterograde and retrograde degeneration occurring after well localised lesions. It is possible to separate the ascending NA pathways into a dorsal and a ventral bundle of axons. The dorsal bundle innervates the cortex and the hippocampus and the ventral bundle supplies NA nerve terminals to the medulla, the pons, the mesencephalon and the diencephalon. The dorsal bundle is found to originate in the locus coeruleus. Lesions of this nucleus abolish the nerve terminals in all cortical areas and in several other areas of the brain indicating a unique role for the locus coeruleus in influencing the activity of the entire brain. The 5-HT pathways have a distribution similar to the ventral NA pathyway. The course of the nigro-striatal and the meso-limbic DA pathways is presented in detail.

Stereotaxic mapping of the monoamine pathways in the rat brain.

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.

The micro-architecture of the substantia nigra was studied in control cases of varying age and patients with parkinsonism. A single 7 mu section stained with haematoxylin and eosin was examined at a specific level within the caudal nigra using strict criteria. The pars compacta was divided into a ventral and a dorsal tier, and each tier was further subdivided into 3 regions. In 36 control cases there was a linear fallout of pigmented neurons with advancing age in the pars compacta of the caudal substantia nigra at a rate of 4.7% per decade. Regionally, the lateral ventral tier was relatively spared (2.1% loss per decade) compared with the medial ventral tier (5.4%) and the dorsal tier (6.9%). In 20 Parkinson's disease (PD) cases of varying disease duration there was an exponential loss of pigmented neurons with a 45% loss in the first decade. Regionally, the pattern was opposite to ageing. Loss was greatest in the lateral ventral tier (average loss 91%) followed by the medial ventral tier (71%) and the dorsal tier (56%). The presymptomatic phase of PD from the onset of neuronal loss was estimated to be about 5 yrs. This phase is represented by incidental Lewy body cases: individuals who die without clinical signs of PD or dementia, but who are found to have Lewy bodies at post-mortem. In 7 cases cell loss was confined to the lateral ventral tier (average loss 52%) congruent with the lateral ventral selectivity of symptomatic PD. It was calculated that at the onset of symptoms there was a 68% cell loss in the lateral ventral tier and a 48% loss in the caudal nigra as a whole. The regional selectivity of PD is relatively specific. In 15 cases of striatonigral degeneration the distribution of cell loss was similar, but the loss in the dorsal tier was greater than PD by 21%. In 14 cases of Steele-Richardson-Olszewski syndrome (SRO) there was no predilection for the lateral ventral tier, but a tendency to involve the medial nigra and spare the lateral. These findings suggest that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of PD.

O. Hornykiewicz

Papers

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

Striatonigral degeneration: Response to levodopa therapy with pathological and neurochemical correlation

Verhalten des Dopamins (=3-Hydroxytyramin) im Nucleus caudatus nach elektrischer Koagulation des Globus pallidus