The role of sigma-receptors in levodopa-induced dyskinesia in patients with advanced Parkinson disease: a positron emission tomography study.

Abstract

Levodopa-induced dyskinesia (LID) in patients with Parkinson disease (PD) mimics acute dystonic reactions induced by antipsychotic agents, possibly mediated by sigma-receptors; however, there are few reports in which the relationship between sigma-receptors and LID in advanced PD is investigated. The binding potential of cerebellar sigma-receptors before and after a pallidal surgery for dyskinesia in patients with advanced PD is assessed. Six patients with advanced PD (male/female ratio 3:3, age 56.7 +/- 9.8 years) underwent stereotactic pallidal surgery (two posteroventral pallidotomy procedures and four deep brain stimulation of the globus pallidus internus, including one bilateral case). Clinical features of patients with PD were assessed using Hoehn and Yahr (H & Y) stages, the Unified Parkinson's Disease Rating Scale (UPDRS), and the Schwab and England Activities of Daily Life Scale (S & E). The LID was evaluated by LID severity score. The binding potential of cerebellar sigma-receptors was determined before and after the surgery by 11C-nemonapride positron emission tomoraphy, a specific radioligand for sigma-receptors in the cerebellum. All clinical scores, especially the LID severity score, were dramatically improved after the surgery (p < 0.05). Preoperatively, contralateral cerebellar binding potential was significantly elevated (p < 0.01), and it was reduced after the surgery, but it was still higher than that of healthy volunteers (p < 0.05). The ipsilateral cerebellar binding potential remained unchanged after the surgery. The level of binding potential did not correlate with H & Y stage, UPDRS, or S & E score, but a strong positive correlation was seen between the binding potential and the preoperative LID severity score when the patients were receiving medication (r = 0.893, p < 0.05). Cerebellar sigma-receptors may potentially involve the genesis of LID in advanced PD.