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Title: Nigral iron and neuromelanin studies in Parkinson's disease
Author: Martin Bastida, Antonio
ISNI:       0000 0004 8511 0814
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Parkinson’s disease (PD) a neurodegenerative condition characterized by the reduction of the pigmented dopaminergic neurons of the substantia nigra pars compacta (SNc) and the loss of the dopaminergic striatal terminals which in turn result in the cardinal motor symptoms including bradykinesia, rigidity and tremor. Iron plays a deleterious role in the pathophysiology of PD due to the generation of reactive oxidative species that leads to oxidative stress and neurodegeneration. In addition neuromelanin is a complex pigment contained in the dopaminergic neurons of the SNc that plays a toxic role in pro-oxidative conditions such as PD. Magnetic resonance imaging (MRI) is a widely available nonionising technique allowing the study of structural properties of the SN such as iron deposition or neuromelanin pigmentation load in PD. In this thesis I have used state of the art neuroimaging to assess nigral iron accumulation and nigral depigmentation in PD, the correlation between neuromelanin decline and nigrostriatal terminal loss, and the potential clinical use of an iron chelation to improve clinical symptoms. The main findings of this thesis are as follows: A) Increased nigral iron accumulation in PD displays an ascendant stratification according to clinical severity at baseline and it is associated with bradykinesia and rigidity symptoms in cross-sectional and longitudinal settings. B) Nigral depigmentation in PD shows a descendant stratification according to disease duration at baseline and displays significant associations with motor severity at baseline and with bradykinesia at follow-up visits. C) The pattern of nigral pigmentation loss shows a ventro-medial pattern and there was a significant correlation between this loss and nigrostriatal terminals decline in the most affected side, but not in the least affected side. D) Finally, iron chelation with deferiprone in PD shows a trend of motor improvement after six months of treatment being optimally monitored with iron-sensitive MR imaging techniques. The results presented in this thesis support the application of multimodal imaging protocols to further understand the dopaminergic pathophysiology of PD and their usefulness for monitoring the progression of the disease.
Supervisor: Piccini, Paola Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral