Presynaptic dopaminergic lesion predicts drug-induced dyskinesia

By Eleanor McDermid, Senior medwireNews Reporter

Research suggests that the extent of presynaptic dopaminergic denervation before starting therapy may predict which patients with Parkinson’s disease (PD) will later develop levodopa-induced dyskinesia (LID).

Phil Lee (Yonsei University College of Medicine, Seoul, Korea) and colleagues studied 127 PD patients who underwent positron emission tomography at the time of diagnosis, before starting drug treatment.

They found that the larger the reduction patients had in dopamine transporter (DAT) uptake in the putamen at baseline, the higher was their risk of developing LID during an average 3.4 years of follow-up. This was true for the anterior, posterior and whole putamen after accounting for confounders, whereas DAT uptake in the caudate and ventral striatum did not predict LID.

When divided into tertiles based on DAT uptake, patients with moderate and severe reductions were respectively 2.97- and 3.47-fold more likely to develop LID relative to those with mild reductions.

The rate of LID in the whole cohort was 27.6% and the rate in those with mild DAT uptake reductions in the whole putamen was about 15% versus 50% in those with severe reductions.

In an editorial accompanying the study in Neurology, Peter LeWitt (Henry Ford Hospital, Bloomfield, Michigan, USA) and Maral Mouradian (Rutgers–Robert Wood Johnson Medical School, Piscataway, New Jersey, USA) say that the findings bring “presynaptic dopaminergic denervation into the forefront for explaining dyskinesia.”

However, they caution that there is as yet no “simple clinical message because of several confounding factors.”

These include a lower rate of dopaminergic agonist use among patients who developed LID, as well as a higher proportion of women. Patients with LID also had higher Unified Parkinson’s Disease Rating Scale scores at diagnosis and were taking a higher average daily levodopa dose.

Indeed, a higher levodopa dose was a significant predictor of LID on multivariate analysis, as was a younger age at PD onset.

“These confounding factors make it difficult to conclude how important the presynaptic dopaminergic lesion is, by itself, for developing LID”, conclude the editorialists.

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