Rich Thompson, Concerning Dr. Iacono s comment concerning the *off* state I would interpret it to mean that the greatest damage is done to the Parkinson brain in the *off* state whether that be before commencing taking sinemet or after where *off* is defined as being incapacitated from the Parkinson s symptoms. In other words if a person does not begin on sinemet after a reasonable amount of time, and continues functioning in a slowed down state , that over time this would be damaging. Don Dr. Don Berns 4943 Del Monte Rd. La Canada, CA 91011 818-790-8812 <[log in to unmask]>