Objective: We wanted to evaluate L-dopa responsiveness in a large cohort of patients with recently diagnosed Parkinson’s disease (PD) using an acute L-dopa challenge test.

Background: L-dopa responsiveness in PD varies, but the determinants of this response are not clearly defined.

Methods: Patients were assessed using the MDS Unified PD Rating Scale motor scale (UPDRS 3), before and after their usual morning L-dopa dose (after overnight omission of their anti-parkinsonian medication). UPDRS components were standardised to a maximum score of 4 for each, to allow for differing numbers of questions. L-dopa response was rated as excellent (≥30% improvement in UPDRS 3 scores) or moderate (<30% improvement in UPDRS 3 scores).

Results: 1008 cases aged 67.4 years (SD 9.1 years) at diagnosis were tested on average 3.3 years (SD 0.9) into their illness. Each of bradykinesia, rigidity and tremor improved significantly after L-dopa (all p<0.001), though the improvement was significantly greater for bradykinesia at 0.35 points, and rigidity at 0.34 points, than for tremor at 0.19 points (both p<0.001). Similarly, lateralised features improved significantly more (0.31 points) compared to axial features (0.12 points, p<0.001). The overall L-dopa response was 30% in 516 cases (51.2%), in whom the mean reduction in UPDRS 3 was 48.4% (SD 14.1), and was <30% in 492 cases (48.8%) whose mean reduction in UPDRS 3 was 12.7% (SD 14.0). Those showing an excellent response were younger (65.9 years, SD 9.4) than those who demonstrated a moderate response (69.0 years, SD 8.4, p<0.001). The baseline UPDRS 3 scores of those showing an excellent L-dopa response (20.6, SD 10.2) were significantly lower than those demonstrating a moderate response (24.4, SD 13.1, p<0.001). The increase in UPDRS 3 score over the preceding 18 months was less in those showing an excellent response at 2.7 (SD 10.7), compared to those demonstrating a moderate response (5.9, SD 10.5, p<0.001).

Conclusions: The response to L-dopa in early PD shows great variation. The magnitude of change is significantly greater for bradykinesia and rigidity than for tremor, and for lateralised (limb) components compared to axial features. The overall motor response is significantly less in older patients. Suboptimal responses are associated with worse baseline motor scores, and faster motor progression rates. Further exploration of the reasons for these observations is needed.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/l-dopa-responsiveness-in-early-parkinsons-disease-results-from-the-united-kingdom-tracking-parkinsons-study/