Centre for Neuroscience - Theses
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ItemNon-motor and extra-nigral aspects of Parkinson’s disease( 2009)Non-motor symptoms and extra-nigral features of Parkinson’s disease, the focus of this thesis, are very common and may result in significant disability. The increased focus on these important clinical features represents a major advance in the care of Parkinson’s disease patients. Chapter 1 provides a state-of-the-art overview of current understanding of the extra-nigral features of Parkinson’s disease, with an emphasis on the underlying patho-anatomical and patho-biochemical substrates. Although most of the discussion pertains to the non-motor symptoms of Parkinson’s disease, the importance of extra-nigral pathology in the pathogenesis of motor problems such as tremor and dopa-unresponsive axial motor features is also highlighted. Chapter 2 focuses on the relative contributions of disease versus medications in producing the non-motor symptom complex of Parkinson’s disease. Chapter 3 provides an original synthesis of the literature on pain, as it relates to Parkinson’s disease, with an emphasis on the putative pathophysiological mechanisms and management of this common and important clinical problem. Chapter 4 contains the major empirical part of the work presented in this thesis. The study provides evidence in support of the hypothesis that pain and dyskinesia (the latter being an almost universal phenomenon in Parkinson’s disease patients treated with levodopa) share common pathophysiological mechanisms in Parkinson’s disease (background discussed in Chapters 1-3). Chapter 5 provides an extensive review of Impulse control disorders and related disorders in Parkinson’s disease (including the Dopamine dysregulation syndrome and punding), problems that are increasingly recognised and frequently complicate (and limit) treatment of the motor symptoms of Parkinson’s disease. Chapter 6 contains an update on Parkinson’s disease therapy (aimed at general neurologists, geriatricians and family physicians), with a critical discussion of the pros and cons of various treatment strategies early in the disease phase, and an emphasis on the management of non-motor symptoms (Table 2 provides a comprehensive and up-to-date summary of the increasing variety of symptomatic treatments currently available for non-motor symptoms). Chapter 7 contains a critical review of the growing literature on the effects of deep brain stimulation surgery (a therapeutic modality that is increasingly being used), on the non-motor symptoms of Parkinson’s disease. It covers not only the neuropsychological and neuropsychiatric outcomes after surgery, but also the impact of surgery on Parkinson’s disease-related sleep, autonomic and sensory disorders. Chapter 8 contains the second part of the empirical work presented in this thesis. This is a case series of 21 operated (mostly bilateral subthalamic nucleus deep brain stimulation) Parkinson’s disease patients, exhibiting Dopamine dysregulation syndrome, Impulse control disorders or punding at some stage during the course of their disease. It provides further insights into the impact of deep brain stimulation on these disorders, currently a very contentious subject (background discussed in Chapters 5-7).