8 Inhibition of COMT reduces cortical motor areas activation in wearing-off Parkinson’s disease patients: An f-MRI study

Abstract

Background Wearing-off (WO) is one of the main problems in levodopa-treated patients. An increased dopamine turnover might play a relevant role in WO pathogenesis. Objective To investigate the modulation of treatment of a COMT-inhibitor in wearing-off Parkinson’s disease (PD) patients regarding cortical motor area activities with f-MRI, we prospectively studied nine PD patients with WO, before and during treatment with entacapone. Methods Nine right-handed PD patients, and 10 age and sex-matched controls were included. Main inclusion criteria were disease duration >5 years, WO and l-Dopa therapy. f-MRI was used to study BOLD signal changes associated with hand movements. A 1.5 T MR system (Signa LX,GEMS) with epibold sequence (TR/TE 3 s/40 ms) and activation map sequences (TR/TE 500/20) was used. For right side, a finger tapping was separately performed, during seven activation blocks interleaved with seven rest periods. In PD-group f-MRI was acquired at baseline and after entacapone introduction. Statistical analysis were performed using SPM2 software. Results The patient group showed a significant response to the COMT-inhibitor. The ON time, based on home diary, significantly improved (hours in OFF: baseline 8.5; last visit at 1 month 6.4; p p p p p Conclusions Our preliminary findings suggest that, in PD patients, wearing-off is associated with the hyperactivation of the primary and secondary motor areas and that entacapone is able to reverse this hyperactivity.