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Hi Mackenzie and others, Sorry that I didn't answer sooner. I have been off list and I also get the digest version of this list which seems to be delayed some days. First of all I want to make it clear that I believe that DBS is a wonderful intervention. As others have posted, whether or not to have DBS is a personal influenced by the guidance of our physician based on our individual situation. I personally started the process to have DBS back in January, but a second neurologist helped me adjust my medication to restore efficacy. I'm sure that I will eventually need to have the procedure down the line. Now to address your post. You wrote>> "What I would like to know is, given that there is a 30% chance of developing dyskinesia after two years of levodopa therapy, and a 50% chance after five years of levodopa therapy, is anyone else disturbed by levodopa being held up as the "best" treatment for PD, the treatment that must be surpassed (by therapies requiring brain surgery, at least) in order for them to be considered successful?" I can't really give a definitive answer. I'm not sure where these statistics came from. The problem with quoting statistics out of context is that you can't assess how valid they are nor what they represent. Are they from a peer reviewed journal? How large was the study? Were the research methods valid? Researchers also like to extrapolate their data in the discussion sections of their manuscripts suggesting that their data show a trend that needs further study. Sometimes these suggestions get promoted by others as study results not something for further investigation.. Now I can only speak from my limited experience with PD over the last eight years, but it seems like the levodopa boogie man is unleashed every time a new agonsist or other PD drug is released. Comtan was hailed as smoothing out the levodopa response; thus, reducing the on/off fluctuations. The theory was that the long term side effects of levodopa were due to fluctuating plasma levels. Comtan would extend the longitudinal effectiveness of levodopa by inhibiting levodopa breakdown in the blood stream. Comtan is a good drug and I take it, but I recently saw a study that appeared to refute the claim that it reduces the fluctuations in plasma levels of levodopa. Neurologist promote the use of agonist alone as the first intervention to supposedly extend the longitudinal benefits of pharmacological interventions. They sometimes throw in that agonists may slow the progression of the disease. It has also been suggested that levodopa use my accelerate progression of the disease. But none of these things have been proven in robust studies. I think that these things come from suggestions that get embellished into results. The bottom line is that it is difficult to separate the beef from the baloney. But enough rambling, get to the point Phil. Theoretically, levodopa is the closest thing we have to restoring normal physiology. Levodopa is a precursor amino acid of dopamine. Theoretically it can be converted into dopamine in the brain and stored in the striatum and globus pallidus and released when the neuron fires. This is contrast to the agonist that sit in the synaptic cleft and statically change the firing thresholds of the neurons. The surgical interventions shut off some of the basil ganglia output all together. So one could speculate that they are disabling function. Indeed as some have posted on the list, DBS doesn't restore normal function. The problem with all the interventions available today is that the disease progresses and thereby reduces the longitudinal efficacy of the intervention. As I mentioned in a previous post, current thinking is that it is the loss of the ability to store dopamine that eventually leads to a reduction in efficacy of levodopa and side effects. This brings me to a final point. I stated in my previous post that DBS had only been in wide spread use for about the last 5 years. Another post made the point that it had been in use in France for 10 years. The Medtronics web site indicates that it has been available since 1996. My point is that 8-10 years ago it was experimental but within the last 5 years it has seen exponential growth as surgeons are trained throughout the world. The Medtronics web site states that 15,000 implants have been performed. The bottom line is that as an intervention it is still in its infancy. The device will continue to improve and the procedure will continue to improve. But that same infancy makes it impossible to predict the longitudinal (long term) efficacy of the device. With the high degree of variability in the progression of the disease itself, it takes a large sample population over a long period of time (10-20 years) to separate out variability in disease progresssion from variability in long term efficacy of the device. We now have a large enough sample population to start conducting meaningful longitudinal studies. So if you have DBS, get enrolled in one. If it indeed is shown to have a limited longitudinal efficacy as is the case with Pallidotomy, it might not make sense to have the procedure as the first intervention. Thus the motivation to ride the drug horse as long as you can - a decision to be made by you and your physician. Now if you go to the Medtronics web site, you will see that response to levodopa is one of the selection criteria for DBS. Why? Because response to levodopa is another indicator that you have idiopathic PD. Idiopathic PD goes along with the substantia nigra cell loss story that results in a dopamine deficiency. Once again replace the dopamine and in early stages symptoms can be relieved. As the disease progresses, dopamine storage in the striatum and globus pallidus is reduced and levodopa is not as effective. But the longitudinal effectiveness of levodopa is highly variable due to the highly variable rate of progression of the disease in each individual. So it's not so much that surgical procedures must "surpass" the effects of levodopa, but that in the absence of side effects levodopa provides the best functional performance. It's replacing dopamine. Remember that the theory behind DBS is that it inhibits output from the basil ganglia. Since we really don't know the function of the basil ganglia, it's difficult to say what function we lose when we shut part of them off. We aren't restoring normal physiology. So until we have sufficient longitudinal data on DBS, it might be best to reserve it for when the medication is no longer tolerable. We have a pretty good understanding of the levodopa devil. When you get a device approved by the FDA, you have to specify the symptomatic indications that it treats. You also need to provide data demonstrating efficacy for those indications. So one set of indications are those associated with idiopathic PD. DBS has also been approved for non-levodopa responsive Parkinsonism indications, such as, dystonia. I don't know all of them, but you can read the web site as well as I can. There are other indications, such as, essential tremor. So you need selection criteria for patients to increase the probability that DBS will be effective for the patient and to be compliant with the use approved by the FDA. Also, failures detract from your efficacy statistics and make your product look bad especially if the patient has an adverse effect, such as, psychosis. Bad for business. The Medtronics web site states that 15% of the PD population could benefit from the device. I don't know how they came up with that. The web site is rather sparse on references. I can speculate that they are basing it on patients that are levodopa responsive, but cannot tolerate the levodopa side effects. I heard an ad on the radio the other day promoting DBS at a local medical center. A local producer recorded his DBS procedure and has made it available on tape. The ad claimed that 87% of the patients that had DBS at this center had dramatic results like Ray. I thought that was cool. We're advertising for DBS surgery. What isn't said is that patients were carefully screened for the procedure and yet 1 out of 10 did not have dramatic results. Just another example of buyer beware. But the good news is that 9 of 10 patients did have dramatic results. DBS needs to be seriously considered when quality of life is affected by medication side effects. Once again a decision for you and your physician. Unfortuantely, levodopa is the closest thing that we have to restoring normal physiology. It does well in the early stages when the disease is dominated by the dopamine deficiency, but it doesn't do anything for the cell loss in the striatum and basil ganglia that eventually dominates and reduces its efficacy. The good news is that there is a lot of reseach exploring the function of the basil ganglia, the factors contributing to cell death, use of growth factor to restore function in the striatum and use of animal models to explore how the basil ganglia develop from conception. So I implore all to get involved in a research study. It gives you the opportunity to stick your nose under the research tent and say "hey, what's going on in here?" Many studies include examination by a research neurologist, so you essentially get a free second opinion on your diagnosis. Much to the surprise of a small number of people, they sometimes discover that they don't have PD. Now wouldn't that make your day! Phil Gesotti 55/ dx 46 ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn