[Motor impairment, in patients with severe Parkinson's disease, associated with dopaminergic hyperstimulation...

[corrected] Entacapone was given to try to improve the motor complications in eight patients with Parkinson's disease (PD) treated chronically with levodopa, with daily severe motor fluctuations and dyskinesias.

We introduced entacapone (200 mg added to every dose of levodopa) to 8 parkinsonian patients (mean age: 68.25 +/- 2.3; range: 68-72; mean PD duration: 10.4 +/- 2.7 years) treated with oral levodopa, plus a dopa-decarboxylase inhibitor (mean dose: 706.25 +/- 2.3 mg/day; mean period of levodopa-treatment; 9 +/- 2.3 years). Dyskinesias were present in all patients (chorea: 8 patients; "off"--dystonia: 4; byphasic dyskinesias: 3). The type and duration (time "on" and "off") of fluctuations was categorized on the "on-off" charts drawn up by the patients or their relatives, and observation by the investigators after the introduction of entacapone. One patient, with severe impairment with entacapone, was evaluated (motor response) during i.v. apomorphine infusion (40 mg, during 3 hours).

The combination of levodopa and entacapone was associated with a net increase in "off" time in all patients (from 5.8 +/- 1.2 h to 12.4 +/- 4.4 h) without change in the URPD. In the patient studied with i.v. apomorphine, "off" periods appeared during the infusion.

These findings suggest that increased daily levodopa consumption may reduce striatal responsiveness to dopaminergic stimulation in severe parkinsonian patients. These data should be considered when planning the treatment strategy of complex parkinsonian patients.