Quantitative Assessment of Motor Response to a Low Subacute Levodopa Dose in the Differential Diagnosis of Parkinsonisms at Disease Onset: Data from the BoProPark Cohort

Abstract

Background: Differential diagnosis between Parkinson’s disease (PD) and atypical parkinsonisms (APs) may be difficult at disease onset. The response to levodopa (LD) is a key supportive feature but its definition is largely empirical. Studies evaluating this issue by quantitative tests are scanty. Objective: We aimed to assess the utility of a subacute low LD dose kinetic-dynamic test in the differential diagnosis between PD and APs. It was applied at the baseline of a prospective follow-up in patients with parkinsonian signs within three years of disease motor onset (“BoProPark” cohort) and eventually diagnosed as PD or APs according to consensus criteria. Methods: Patients under at least 3-month LD therapy received a first morning fasting dose of LD/benserazide or carbidopa (100/25 mg) and underwent simultaneous serial assessments of plasma LD concentration and alternate finger tapping frequency up to 3 h. The main outcome was the extent of LD motor response, calculated by the area under the 3 h tapping effect–time curve (AUC_ETap). A receiver operating characteristic (ROC) curve analysis was performed to establish the optimal AUC_ETap cut-off to differentiate PD and APs. Results: The first 100 consecutive “BoProPark” patients were analyzed. Forty-seven patients were classified as possible, 37 as probable PD and 16 as APs. AUC_ETap medians were similar in the PD subgroups but reduced to a third in APs (p < 0.001). The optimal AUC_ETap cut-off value was >2186 [(tap/min) x min], with a sensitivity of 92% and a specificity of 75%. Accuracy of the test was 0.85 (95% CI 0.74–0.95), p < 0.0001. Conclusion: The estimation of 3 h AUC_ETap after a subacute low LD dose proved a reliable, objective tool to assess LD motor response in our cohort of patients. AUC_ETap value rounded to ≥2200 supports PD diagnosis, while lower values may alert to AP diagnoses.