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The Lewy body
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    James Parkinson noted: “A diseased state of the medulla spinalis, in that part which is contained in the canal, formed by the superior cervical vertebrae, and extending, as the disease proceeds, to the medulla oblongata . . .is the proximate cause.”1

    In the late 19th century, because knowledge of the pathophysiology of the basal ganglia was imprecise, Gowers and others implicated the motor cortex as the source of Parkinson's disease. Edouard Brissaud (a neurologist's neurologist) in 1894 thought that the site of Parkinson's disease must be peduncular or subthalamic, rejecting prevalent theories that it was muscular or a neurosis. He reported a parkinsonian syndrome caused by a tuberculoma of the substantia nigra and concluded.2

    “The locus niger might well be its anatomical substratum.”

    In a vital paper, Tretiakoff in 1919 examined the brains of nine parkinsonian patients. He was the first to state that substantia nigra lesions were important in both Parkinson's disease and in postencephalitic patients, a view supported by Greenfield. Tretiakoff3 noted in particular, reduced numbers of pigmented cells in the locus niger, which he related to a disorder of muscular tone in Parkinson s disease. He also found peculiar concentric inclusions in the cytoplasm of these nigral cells. A more detailed study of mid-brain neuropathology by Foix and Nicolesco4 in 1925 completed the anatomical picture, which so frustratingly had eluded James Parkinson.1

    However, these inclusion bodies had already been described by Friederich Lewy (1885–1950)5 who discovered them in 19126 while working in Alzheimer s laboratory.7 They proved to be the hallmark of Parkinson's disease.8

     Lewy described chronic cell atrophy and glial overgrowth in the putamen and globus pallidus, with reduction of fibres in the ansa lenticularis. These he likened to the lesions of senility. Later, in 1923, he observed9 that most of the atrophic cells showed a senile fibrillar change, and emphasised the great cellular loss in the pallidum, the dorsal nucleus of vagus (vegetative oblongata nucleus) when there was tremor of the larynx, and also stated that cells of the substantia nigra are regularly involved. The characteristic, but non-diagnostic Lewy bodies remain the major features10 on microscopic examination.11 Lewy found them most strikingly in the nucleus basalis, substantia innominata, and in the dorsal motor nucleus of the vagus, but less often in the substantia nigra. Subsequent studies showed them in neurons carrying neuromelanin pigment: the locus coeruleus, autonomic ganglia, amygdala, and hypothalamus. They can be seen throughout the cortex in smaller numbers.

    A cautious observer, Lewy wrote:

    “They (intracellular inclusions) are simply findings which I up till now have found in all cases of paralysis agitans that I have examined, but which were absent in the other (control) cases.”

    Lewy knew little of the biology of neuromelanin. We now know it may be the result of breakdown of intracellular catecholeamines, including dopamine, but whether it protects the cell or is itself toxic when it accumulates is uncertain. It is of interest that neuromelanin is preserved in albinos. Lewy bodies are circular eosinophilic structures with a dense protein core surrounded by a peripheral halo located within the cytoplasm of neurons The ultrastructural appearance is like a sunflower with a dense central core of circular shaped structures and a rim of radiating filaments (7 to 20 nm in diameter), the largest filaments at the periphery, which corresponds to the halo. Their size and number vary. Lewy bodies result from neuronal degeneration, with accumulated altered cytoskeletal elements that stain with antiubiquitin antibodies and antibodies to neurofilaments.

    Lewy stressed that they were not confined to Parkinson's disease. About 5% to 10% ofasymptomatic people have Lewy bodies, usually in the substantia nigra.12 Later work showed that they occur in other neurodegenerative disorders including the nosologically ambiguous dementia with Lewy bodies.13


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