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You will find a citation of Bateman's letter in my current (December) post of Current Science Reviews, posted here earlier this month. In that series my policy is to present everything I can find, trying not to be selective, partial, or judgemental. I infer that the letter in question is just an observation by a practicing physician, and not the product of an organized research program, so it's not surprising that its conclusions may be incomplete, or deviate from conventional wisdom, and they should be taken only at face value. PS: If you haven't done so, you may be interested in checking the listserv archives for past issues of the Reviews, which go back over a year now. Cheers, Joe J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks CA 91403 On Wed, 13 Dec 1995, Delana Vaughan wrote: > I have just read a Leter to the Editor in the > J.Neurol.Neurosurg.Psychiatr.1995;59:555-565 by D.E. Bateman. The title is "A > simple model to explain the motor fluctuation seen in Parkinson's Disease." > This letter presents a very interesting explanation for the "on/off" > phenomenon where PD is described as a 2-stage disease with a stable response > period and an end of dose deterioration response period. The model assumes a > constant amplitude and duration of central dopaminergic stimulation due to a > fixed dose of L-DOPA throughout the course of the disease. The model predicts > a threshold of central dopaminergic stimulation for "on". In early disease, > the amount of stimulation is always above threshold so wearing off is not > apparent. With progression of disease, there is a faster wearing off from"on" > due to the differences in the amount of stimulation above the threshold and > not due to any changes in the dose response curve. In early disease the > considerable stimulation above threshold "conceals" any wearing off from > "on", whereas later, when the patient is completely dependent on the plasma > concentration of L-DOPA with no storage of dopamine, "off" appears between > doses. The main conclusion is that the duration of L-DOPA treatment is > irrelevant to the development of motor fluctuations implying that > "withholding L-DOPA treatment for as long as possible may deprive patients > of a period of benefit without complications". > > My question to you: the author includes dyskinesia in the model sketch and > shows the threshhold for its appearance to be lowered with progressive > disease but he never actually discusses dyskinesia with respect to the model. > It's a very important consideration since most believe dyskinesia increases > with increased use of L-DOPA. Please go read the letter, check out the model, > and let's discuss our individual interpretations here. Can you figure out > what relationship dyskinesia has to the model since it's not discussed in the > text? Maybe we should write and ask the author to clarify. > > Thanks. I think you'll find this a challenge worth pursuing. > > Delana Vaughan >