ONPRC Symposium Presentation

Editor's Notes

• #2: Notice: The notes under the slides are sometimes just for my own information, not necessarily what I said during the presentation.
• #3: Medication supplementing dopamine supply is the first treatment option, but as the disease progresses the medication becomes less effective and the person experiences more motor fluctuations and side effects (involuntary movements, dyskinesia)
• #4: The basal ganglia is the part of the brain that controls movement. With the lack of dopamine, some groups of cells have abnormal activity, which can be suppressed with electrical current. Before DBS, the uncooperative cells would just be killed or removed (lesion). The stimulation can be turned off if negative effects are experienced. If there is a problem with the hardware such as infection the electrodes can be removed, damage to the brain is minimal. This option is much more desirable than lesions, because they are not reversible. Tremor, bradykinesia, and rigidity are immediately and noticeably improved with DBS, but affects gait and balance in more subtle ways, and may take longer to present. Changes in gait and balance are more difficult to see, but are important because impaired gait and balance increases the risk of falls. For this reason, quantitative data is required.
• #5: Most of these are closely related to quality of life, but also to risk of falling and injury. For example, if you are walking too slowly you are more likely to fall, and even if you don’t fall it may be difficult to keep up with others. PD patients sometimes turn too fast and without adequate base of support. Freezing of gait is a common problem among people with Parkinson’s, and most commonly occurs during turns or walking through doorways. The metrics relating to gait initiation and turning help us understand how medication and DBS affect the probability of freezing.
• #7: Most people, especially clinicians of course, use clinical scores. We also had trained clinicians rate the severity of symptoms before each test session.
• #9: Accelerometers are capturing the movement, and the gyroscopes record the angle. We used this system because the data can be collected anywhere. You do not need a big lab with motion capture cameras, this is much faster, easier, and cost effective. In fact, some of the data for this project was collected in intensive care the day after surgery.
• #10: ISAW: stand quietly for 30 seconds (measure balance), walk normally for 7 meters (gait initiation and normal gait), turn around (turn), walk back (gait), stop and hold (gait termination) A lot of information is gathered from just one exercise. The targets on the person show which sensors are used to analyze each part.
• #11: Notice that beyond 30 days after surgery, the DBS is always left on. Also, even though we started with 80 people, not everyone was able to complete all of the test sessions, so the numbers quickly dwindled. Another limitation is that in our analysis (in order to use rmANOVA), only people with all of the time points and conditions could be included. For this reason, the post surgery data includes everything beyond 30 days. Feasibility study. It was a convenient sample, just got the data when they came in for usual clinic appointments. Not a traditional study where all of the time points are pre determined. More exploratory.
• #12: Data organized based on testing condition (on or off medication, on or off dbs) as well as session (pre surgery, 30 days, 90 days). Data availability affected groupings. While many participants had data for off both medication and dbs at 30 days, none had this condition at 90 days. To get an idea of what I was working with, first I created plots showing the means with standard error bars, and looked at the distributions.
• #13: The next few slides will have this format. Left graph = GPi, Right graph = STN. The left side of each graph is pre surgery (on and off meds), and the right side is post surgery (on and off meds, DBS on the whole time). The columns show the mean of each condition, the error bars show standard error, the horizontal lines show significant differences with p-values. The change in UPDRSIII shows the overall improvement of motor symptoms. Symptoms are better with medication, dbs, or both in STN. For the GPi group DBS alone did not significantly reduce symptoms, but there certainly appears to be a relationship.
• #14: Medication causes an increase in RMS sway (sway dispersion), which decreases postural stability. However, after surgery the RMS sway is always better for the GPi group, regardless of medication. STN stimulation did not appear to have an effect.
• #15: With the GPi, you can see that the stride length significantly increases with mediation alone, DBS alone, and the combined therapies compared to the off state. However, there is no improvement in best states, but DBS seems to have as much effect as medication. Improvement does not occur for STN, with the stride length returning to pre surgery off levels regardless of the therapy used.
• #16: The GPi stimulation is more effective at decreasing turn duration. While there is a similar decrease in the STN group, there is more variability, so the difference is not significant.
• #17: The bold metrics are ones I showed you. Green indicates an improvement, red indicates a decline. The red markers also have an x in case anyone is color blind. Gait was most negatively affected by DBS, especially with the STN target. Arm swing velocity was worsened by both. GPi was more beneficial in all but centroidal frequency in the ML direction and arm range of motion.
• #18: Mention clinical correlations in last point.