Levodopa Challenge Test

It can be difficult to accurately differentiate PD from other forms of parkinsonism, especially during the early stages of disease. Levodopa administration can be used for diagnostic purposes, as PD patients respond more frequently and robustly to levodopa compared with other forms of parkinsonism.

Clarke and Davies (145) reviewed 13 studies that examined whether an acute levodopa or apomorphine challenge test could aid in the diagnosis of PD. Four studies examined de novo patients and nine examined patients with clinically established PD. Although there was significant variability in the methodologies employed, abstracted sensitivity and specificity data were summarized from the studies and the two challenge tests compared as to their ability to accurately predict patients' diagnosis. The sensitivity for the diagnosis of established PD for apomorphine was 0.86 [95% confidence interval (CI)], acute levodopa 0.75 (95% CI), and chronic levodopa therapy 0.91 (95% CI). The specificity for the diagnosis of established PD was apomorphine 0.85 (95% CI), acute levodopa 0.87 (95% CI), and chronic levodopa therapy 0.77 (95% CI). The number of patients positive for each test divided by the number with clinically diagnosed de novo disease was apomorphine 0.63 (95% CI), acute levodopa therapy 0.69 (95% CI), and chronic levodopa therapy 0.76 (95% CI). Three of the studies allowed for the possibility to cross correlate agonist or acute levodopa with chronic levodopa therapy. Twenty-one chronic levodopa patients described as having a positive response initially had a negative result with acute levodopa. The authors concluded that the accuracy of the acute levodopa and apomorphine tests was similar but not superior to that of chronic levodopa therapy, and that these were not more accurate than the established accuracy of clinical diagnosis of PD (75-80% accuracy). In addition, given the additional costs and adverse effects associated with their use, they could not recommend using the challenge tests.

Rossi (146) reported the use of acute challenges with apomorphine and lev-odopa in patients with clinically defined forms of parkinsonism to assess the potential accuracy of the tests in making a diagnosis. Motor responses to the acute administration of levodopa and apomorphine were analyzed in a series of 134 parkinsonian patients (83 with a clinical diagnosis of PD, 28 patients with multiple system atrophy (MSA), 6 with progressive supranuclear palsy, and 17 unclassified patients). The duration of disease or the clinical stage of the patients was not described. UPDRS motor scores were evaluated one hour following levodopa administration and 20 minutes after apomorphine injection. The motor evaluation was matched with the clinical diagnosis and the response to chronic levodopa therapy. Those patients who had improvement of at least 16% on the UPDRS were more likely to have PD when compared to non-PD patients. When comparing PD with

MSA patients, those who improved at least 18% on the UPDRS were more likely to have PD rather than MSA. If a patient responded to the challenge test with at least a 14.5% improvement in UPDRS, they were more likely to respond favorably to chronic levodopa therapy. The authors conclude that use of the challenge test was helpful in making treatment decisions regarding long-term levodopa therapy. It appears that, overall, an acute levodopa test is not very useful in improving our ability to diagnose PD. Questions remain about its use in making treatment decisions.

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