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

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 >5years, WO and l-Dopa therapy. f-MRI was used to study BOLD signal changes associated with hand movements. A 1.5T MR system (Signa LX,GEMS) with epibold sequence (TR/TE 3s/40ms) 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 1month 6.4; p <0.01). The hand movements differed compared with controls numbers of execution/time: 26+2.1/min (PD) vs 40+4.4c/min (controls). In baseline condition, compared to controls, bilateral M1 areas showed activations with a main BOLD signal increase in the area contralateral to finger tapping (p <0.001). Moreover, in premotor areas both contralateral PMC and SMA showed an increase in activation with respect to controls. During entacapone therapy, regarding finger tapping of the right hand, the activation of the contralateral M1 was detected but less evident than at baseline (cluster volume: 406 vs 1462; p <0.001), where ipsilateral M1 did not show any difference. In premotor areas both contralateral PMC (cluster volume: 100 vs 50; p <0.001) and SMA showed a reduction in activation (cluster volume: 147 vs 54; p <0.001). Unlike baseline condition, ipsilateral PMC showed a significant activation (cluster volume: 65 vs no activation). 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. [Copyright &y& Elsevier]