Dyskinetic patients show rebound worsening of affect after an acute L-dopa challenge

Abstract

BackgroundMotor response complications that arise with repeated L-dopa administration for the treatment of Parkinson’s disease are well understood but the relationship between motor response complications and affect are not. We proposed that patients with dyskinesias would report rebound worsening in affect during wearing-off of L-dopa effect. MethodsFifty Parkinson’s disease patients with were assessed with the Purdue Pegboard test and rated Positive Affect and Negative Affect after overnight withdrawal of dopaminergic medications and half hourly for 6 h after a standard L-dopa challenge. Patients were carefully classified into stable responder (n = 12), fluctuator (n = 15), and dyskinetic (n = 23) groups. ResultsPositive Affect was improved by L-dopa in dyskinetics and to a lesser degree in fluctuators but not in stable responders. At T = 4–6 h, Positive Affect rebounded below baseline in dyskinetics only. On regression analysis, rebound worsening positively correlated with ratings of dyskinesia severity. Negative Affect improved with L-dopa in all groups and tended to remain below baseline for 6 h after L-dopa challenge. Peak effects of L-dopa on Positive Affect and Negative Affect occurred significantly earlier than effects on Purdue Pegboard test and were positively correlated with L-dopa equivalent daily dose. ConclusionThere is a clinical dissociation between L-dopa effects on motor function, Positive Affect and Negative Affect. Rebound worsening in Positive Affect occurred only in dyskinetic patients and the onset of rebound worsening occurred before the end of the motor benefit phase. These observations could explain why some Parkinson patients report wearing-off symptoms despite the external impression of good motor control.