Targeting Hypokinesia in Parkinson's Disease with Quantitative Measures and a Computational Model to Determine Its Severity, Its Improvement from Therapy, and Explore Underlying Pathophysiological Mechanisms

Hypokinesia is one of the most disabling movement abnormalities caused by Parkinson's disease (PD). It is a clinical term that refers to the general reduction of mobility experienced by people with Parkinson's disease (PWPD). Hypokinesia affects movements in three ways: 1) movements are slow 2) movements are performed with reduced amplitude compared to what is required for the task and 3) it takes longer for PWPD to initiate movements. All of these impairments affect the ability of PWPD to perform common daily activities and can cause feelings of frustration and anger that may lead to altered self esteem, depression, and a reduction in their quality of life. Although effective treatments do exist for well-selected patients, there are many avenues open for improving current treatments, identifying new treatments, and understanding mechanisms of hypokinesia that could potentially lead to more effective therapies and greatly impact the lives of PWPD. In this dissertation we sought to improve current treatments and provide opportunities for future treatments for hypokinesia by addressing three important clinical questions relating to hypokinesia. First, are there immediate improvements in hypokinesia from a surgical procedure called deep brain stimulation (DBS) that can be measured during surgery and used to help guide surgical decisions and optimize clinical outcomes? Second, can we determine what types of movements are affected by hypokinesia in early stage, untreated PD in order to provide an objective metric used to assess an emerging treatment for PD? Third, might perceptual deficits that are linked to sensory processing impairments play a role in the manifestation of hypokinesia? If so, targeting these deficits may provide new and better therapies. We addressed these questions by using the quantitative and computational techniques outlined in the next three paragraphs. A common treatment for advanced PD is a surgical procedure called DBS. The surgery is performed on awake patients, and it entails surgically implanting electrodes (leads) that provide chronic stimulation to the affected brain area that controls movement. Although the treatment is almost always effective, the degree of improvement in hypokinesia varies among patients. The accuracy of the placement of the DBS lead in the affected area is believed to have the most effect on the improvement of hypokinesia. We suggest that using quantitative measurements of hypokinesia to evaluate the efficacy of the location of the DBS lead in improving hypokinesia during the surgical procedure might therefore improve the overall clinical outcomes. The surgical team would then have objective, accurate measurements of the degree of improvement in hypokinesia during the surgery, when the lead's position in the brain could be modified to achieve optimal results. Therefore, we designed a prospective study to measure upper extremity hypokinesia using a quantitative measure of angular velocity. Analysis of 98 DBS procedures performed on 61 patients showed that on average there was an 81% improvement in quantitative measures of hypokinesia from implanting and activating the DBS lead (p