Dyskinetic Parkinson's disease patients demonstrate motor abnormalities off medication

Abstract

The pathophysiology of L-dopa-induced dyskinesias (LIDs) in Parkinson's disease (PD) remains poorly understood. The presence of superimposed LIDs clearly differentiates motor performance of dyskinetic from non-dyskinetic PD subjects when they are on medication, but here, we investigated whether their respective motor performance differs while subjects are off L-dopa medication and LIDs are not apparent. We assessed the motor performance of nine dyskinetic and ten non-dyskinetic PD subjects off L-dopa, and of ten age-matched control subjects, during a visually guided tracking task. As previous studies have suggested that linear dynamical system (LDS) models are useful to assess motor performance in PD in addition to overall tracking error, we used LDS models to assess the damping ratio parameter of motor behavior while controlling for disease severity. While overall tracking error did not significantly differ across groups, dyskinetic PD subjects demonstrated a significantly decreased mean damping ratio compared with control and non-dyskinetic PD subjects. For both groups, greater disease severity significantly predicted a lower damping ratio, but even after controlling for disease severity, the damping ratio for dyskinetic subjects was significantly lower. Our results demonstrate, somewhat counter-intuitively, that motor performance of dyskinetic and non-dyskinetic PD subjects differ, even off L-dopa when no dyskinesias are seen. A decreased damping ratio is indicative of a tendency to overshoot a target during motor performance, similar to the dysmetria found in cerebellar patients. We discuss the possibility of motor abnormalities in dyskinetic PD patients off medication in relation to altered functional cerebellar changes described in PD.