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Title: The role of the pedunculopontine region in basal ganglia mechanisms of akinesia
Author: Munro-Davies, Lisa Edana
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1999
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There has in recent years been a resurgence of interest in the treatment of Parkinson's disease by stereotactic surgical techniques. The phenomenal success of levo-dopa in the 1960s led to the virtual disappearance of surgery for Parkinson's Disease. However, two decades after its introduction the problems associated with the long-term administration of levo-dopa became well recognized. Over the same period the advance in our knowledge of the neural mechanisms underlying parkinsonian symptoms has been remarkable. Studies established that the loss of the nigro-striatal dopaminergic projection results in overactivity of the GPm and SNr inhibitory output, which in turn depresses the motor activity of thalamic and brainstem structures to which they have been shown to project, thus leading to the clinical manifestations of parkinsonism. It has long been assumed that the increased inhibitory output of the GPm acts via the thalamocortical feedback route to produce akinesia. However, this view fails to explain the clinical and experimental observation that thalamotomy, despite relieving tremor, rarely improves akinesia. Conversely medial pallidotomy may alleviate akinesia but has a lesser effect upon tremor, whereas high frequency stimulation or lesioning of the STN improves both symptoms. As thalamic lesioning does not affect the descending outputs of the basal ganglia, whereas pallidotomy and subthalamic nucleotomy do, a logical conclusion would be that overactivity of descending projections to the pedunculopontine area in the upper brainstem, rather than the overinhibition of the thalamic motor nuclei, is responsible for the akinesia of Parkinson's Disease. Therefore I have studied the effects of lesions of the PPN on movements in monkeys. The results establish that in the normal monkey a unilateral lesion of the PPN will result in a temporary akinetic state, whereas bilateral PPN lesions will generate a lasting Parkinsonian like akinesia. Results are consistent whether the lesioning method is by radiofrequency thermocoagulation, or by pressure injection of a neuron specific excitotoxic agent. Clinically, I have worked with the Oxford Movement disorder group studying the effects of lesioning, and deep brain stimulation in the basal ganglia of Parkinsonian patients.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Parkinson's disease