New Treatments for Movement Disorders. Part 3

Ophthalmotomy was a major treatment back then. It was with the advent of levodopa that we saw the waning of surgical treatments for Parkinson’s disease, and in 1992 we saw a renaissance of the surgical treatments. These surgical treatments have gone mad, as have other treatments that have been explored. Let’s review them, shall we? Now this was also there in 1992, maybe a little bit after. Amantadine is an agonist, Symmetrel, that was originally designed as an antiviral. It has mild dopamine agonist activity. It’s a marvelous drug. Little pearl on the side; I like to use amantadine in early disease or even in late disease, for whatever reason they get like two or three months of, you know, you don’t want to increase the levodopa because they get dyskinesias or they get confused or psychotic. You don’t want to add an agonist for the same reasons. Oh, what to do? So I give them a little bit of amantadine. It helps, it energizes them. Just like in MS. I don’t know why. Maybe it’s the antiviral thing. Maybe Parkinson’s is a viral disease, I don’t know. Who knows. Vitamin E, sure why not? Two thousand units, can’t hurt. Levodopa both the controlled release and regular format. Is the controlled release all that advantageous? Well, because it smoothes out the response, it smoothes out the levodopa concentrations. There’s this one woman, a practicing parkinsonologist, this same woman comes from DuPont every single week to tell me, “Did you realize that the controlled release preparation of Sinemet really smoothes out levodopa level during the course of the day? And that’s because of its controlled release, enteric preparation.” “Joanne, I know.” Next week, “Did you know …” it’s some kind of a plan, it’s a plot.

Various dopamine agonists that I’ve reviewed for you, the CO and T inhibitors, the two major ones right now, tolcapone which does cross the blood-brain barrier, entacapone which does not. Growth factors coming out. I don’t want to spend a lot of time on that. If you want to read about it, my appendix in 9 font will tell you all about it. Thalamotomy, pallidotomy; now we are going to talk a little bit about this. To understand these surgeries one has to understand this model for basal ganglionic function. Remember now where we have come in surgical ablation treatments in Parkinson’s disease. The story goes back to the 1930’s. Neurosurgeon, ” I see a person with parkinsonism, a right hemibody parkinsonism with tremor and stiffness. My solution to this is very simple. I will completely ablate the left motor cortex. This should fix everything. That is what I think because I am a very powerful neurosurgeon. I think that if I take out the entire motor cortex on the left side this will certainly help his parkinsonism.” And they did this, in point of fact. Brilliant, absolutely brilliant. Complete paralysis but no more parkinsonism. It was about at that level of sophistication. With the advent of that amazing story of MPTP and the availability of MPTP in a monkey model, in which you can stick probes in there and try and figure out what’s going on in different centers in the brain, now we can start to forge a new model for an understanding as to why putting holes in certain parts of the brain could conceivably relieve the cardinal aspects of idiopathic Parkinson’s disease. And that was the major advance between 1968 and 2006, or 2006, in terms of understanding how it is that pallidotomy, for example, for subthalamic lesions can work. That’s the first point. The second point is, curiously enough – I don’t understand it – but electrical stimulation of a site at high frequency can accomplish the same end as a larger lesion in the same locale. I don’t understand why. I like to watch people get up and try to explain. These are formidable people. Big. Mark Halleck. Did you see Mark Halleck’s platform two years ago? He understands dystonia now. Amazing. Mark Halleck is not to be trifled with. You get Mark Halleck on your tail in a conference, you are not in good shape. So Mark Halleck gets up there and he starts explaining this stuff and he thinks we understand. We don’t, of course, but we are coming closer it seems to me, and it’s a function really of understanding some of these connections, which I now want to draw for you.

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