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Regional substantia nigra selectivity in the pathology of movement disorders

Fearnley, Julian Michael; (1991) Regional substantia nigra selectivity in the pathology of movement disorders. Doctoral thesis (M.D), UCL (University College London). Green open access

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The micro-architecture of the substantia nigra was studied in controls and patients with parkinsonism. The pars compacta of the caudal nigra was subdivided into 7 regions and morphometry was performed on a single section. In 36 control cases, there was a linear fallout of pigmented neurons with advancing age at a rate of 4.7% per decade. Regionally, the lateral ventral tier was spared (2.1% loss per decade) in comparison to the medial ventral tier (5.4%) and the dorsal tier (6.9%). Qualitatively, the most severely affected regions were the most pigmented. In 20 cases of Parkinson's disease, there was an exponential loss of neurons with increasing symptom duration. Losses were greatest at the beginning of the disease and tailed off as it progressed. In the first decade there was a 45% loss, ten times greater than could be accounted for by normal ageing. Regionally, the pattern was opposite to ageing and cell loss was greatest in the lateral ventral tier (average loss 91%) followed by the medial ventral tier (71%) and least in the dorsal tier (47-50%). This pattern was only seen in Parkinson's disease. In 15 cases of striatonigral degeneration, there was a similar predilection for the lateral ventral tier, but greater involvement of the dorsal tier (average loss 68-79%). In 14 cases of progressive supranuclear palsy, involvement was greatest in the medial nigra and least in the lateral nigra. In Parkinson's disease, the length of the presymptomatic phase from the onset of neuronal loss was approximately 5 years. At the onset of symptoms, average losses were 48% in the caudal nigra and a 68% in the lateral ventral tier. The presymptomatic phase is represented by incidental Lewy body cases: individuals who die without any sign of parkinsonism or dementia, but who are found to have Lewy bodies at autopsy. Substantial neuronal loss was found in 7 incidental cases disproving the hypothesis that incidental Lewy bodies may be a feature of normal ageing. Furthermore, loss was confined to the lateral ventral tier (52% loss) in a pattern similar to Parkinson's disease. This study confirmed selectivity of Parkinson's disease within the substantia nigra using regional morphometry. It provides evidence that ageing is not important in the pathogenesis of Parkinson's disease. It also supports the notion that incidental Lewy bodies are indicative of presymptomatic Parkinson's disease.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Regional substantia nigra selectivity in the pathology of movement disorders
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Movement disorders
URI: https://discovery.ucl.ac.uk/id/eprint/10122274
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