Response to brief levodopa infusions in parkinsonian patients with and without motor fluctuations

The fluctuating response to levodopa may result from progressive loss of striatal dopamine terminals and consequently increasingly impaired dopamine storage capacity. This hypothesis predicts that the acute response to levodopa would shorten with increasing disease severity. To test this, we compared the duration of improvement in tapping and walking speeds following discontinuation of 2-hour levodopa infusions in nine previously untreated (UT), seven stable (ST), and 17 fluctuating (FL) subjects. Mean Hoehn and Yahr disability in the morning prior to levodopa infusion was 2.8.2.2, and 4.4 for UT, ST, and FL subjects. Six of nine UT, six of seven ST, and all FL subjects exhibited improvement with the infusions, which produced similar peak plasma levodopa levels in all groups. The duration of the response was similar in the ST and FL groups. The response in the UT group was heterogeneous; in three, the response was of similar length as compared with the ST and FL groups, but was longer in the other three UT subjects. The correlation between disease severity and response duration was poor. The ST and FL groups, while differing in disease severity, exhibited a similar duration of response to levodopa infusion. This does not support a reduced dopamine “storage capacity” as the sole explanation for the length of the short-duration response. Furthermore, motor fluctuations appear to be present from early in treatment, but only become noticeable when ‘off’ disability becomes marked.