Effects of chronic levodopa and pergolide treatment on cortical excitability in patients with Parkinsonʹs disease: a transcranial magnetic stimulation study

Objectives: Transcranial magnetic stimulation was used to assess the effects of chronic levodopa and pergolide treatment on motor cortex excitability in Parkinson disease (PD). Methods: Motor thresholds, intracortical inhibition and facilitation were studied at baseline and after 6 and 12 months of therapy in 10 PD patients and compared to 7 age-matched controls. Results: At baseline, there was significantly less intracortical inhibition with only a slight reduction of intracortical facilitation in PD as compared to controls. Relative to pretreatment condition, levodopa restored intracortical inhibition for 12 months while pergolide did not. Intracortical facilitation was always within the normal range. Motor thresholds were unchanged in both groups of patients over 12 months. Clinically, levodopa and pergolide improved motor Unified Parkinsonʹs disease rating scale (UPDRS) scores at 6 months but only levodopa maintained benefit at 12 months as compared to baseline. Conclusions: Levodopa and pergolide differentially affected cortical inhibitory circuits at 12 months. The progressive deterioration of restored intracortical inhibition with pergolide may be due to the development of tolerance and down-regulation of dopamine receptors.