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HI Brian, I have not read your Engineers model of brain and Sinemet - at least in the past few months (As I recall you wrote it a year or 2 ago and I think I read it then). I think that the major reason for not using Sinemet early has to do with the development of dyskinesia which usually doesn't take place until after 2-4 years on the drug. I know mine started after about years on the drug and by 5-6 years it was becoming by itself disabling. I agree with you that the death of the nigral cells is the primary reason for the worsening of symptoms but one can push the remaining cells with L-DOPA in combination with the agonist harder later if you don't have a severe dyskinesia as your limiting factor (as I do). Does that make sense? If your understanding of the pathophysiology is different please let me know. Neurology is not my primary training and I could (easily) be misinformed on this. Brian Collins wrote: > > For Charles T Mayer, M. D. > > Hello Charlie, you wrote previously :- > > > Most movement disorder specialists I think- try to avoid > > Sinemet early in the disease because it can cause dyskinesia > > (random jersey movements) after several years of use but it is > > clearly the most effective drug. > > I noticed that you omitted to say what your view is on this subject. > I, as you may be aware, am firmly wedded to the view that the cause > of so-called 'fluctuations' and apparently unpredictable switches of > symptoms from On to Off etc is caused simply by the fact that we continue > to lose dopamine cells, and the margin of tolerance gets smaller and > eventually reaches zero. This theory answers all known characteristics > without the need for some tenuous link (I have yet to see an explanation > of how it works) between early and late phases of PD. > Any thoughts ? Have you by any chance read the description of my 'Engineer's > Model of the brain and Sinemet? > > http://james.parkinsons.org.uk > Regards, > -- > Brian Collins <[log in to unmask]> -- ****************************************************************************************** Charles T. Meyer, M.D. Middleton (Madison), Wisconsin [log in to unmask] ******************************************************************************************