Parkinson’s is more than a motor disorder that responds to dopamine replacement. Dopamine non-responsive features account for much of the disability that develops with disease progression. For example, gait and balance deficits become increasingly severe disabilities. These features tend to respond poorly to dopamine replacement. The precise abnormalities in brain function related to these features are not well understood. Our approach combines MRI, PET scanning, and measure of gait and balance to improve understanding.
Treated patients with Parkinson’s and gait or balance symptoms will be recruited. A group of normal subjects of a similar age range will also be studied. A comprehensive gait assessment will be performed by having patients walk on a computerized mat with embedded microswitches that captures information such as stride length, step to step variability, etc. Postural stability will be assessed with a computerized system that assesses response to situations requiring a sudden shift in motor activity to prevent falls. PET scans will be done to assess the status of the dopamine systems in the brain. Advanced MRI studies using a high field magnet (4.7 tesla) will be used to assess structures of the brain that are know to be involved in the generation of normal gait.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Impaired gait and balance, with the associated high risk of falls, are major sources of disability in Parkinson’s. This study will help understand the association between these symptoms and abnormal brain structure and function. By clarifying our understanding of the brain changes that produce these debilitating features of Parkinson’s, we hope to establish new targets for medical and surgical approaches to improve gait and balance thereby improving patients’ independence and mobility.
We anticipate that this study will confirm that changes in gait and balance that do not respond well to dopamine replacement are associated with impaired function in parts of the brain that are remote from dopamine pathways. In particular, we expect these features to be associated with changes in motor cortex (supplementary motor area) and midbrain (pedunculopontine nucleus), but not in dopaminergic parts of the brain like the substantia nigra.
In order to evaluate the specific aspects of walking and balance that respond to medications, we are evaluating, in detail, the walking patterns and balance control of people with PD. We are using magnetic resonance (MR) imaging and spectroscopy and positron emission tomography (PET) scans to measure the changes in the brain that occur in PD. Balance testing and assessment of gait patterns are done when people have taken their PD medications and again when they have not taken them for 12 hours. All the assessments and scans need to be done within an 8 week window. Due to some technical difficulties with the PET scans, there was a delay in starting the project. To date, we have enrolled and completed assessments for 4 subjects with PD and 4 control subjects. Three more PD subjects will be seen in the third week of January and recruitment is continuing so we can meet our goal of 40 subjects with PD and 20 control subjects.