People with Parkinson’s disease whose motor symptoms are eased by levodopa (L-DOPA) therapy may be “more likely” to develop earlier in their disease course the abnormal involuntary movements known as dyskinesia than do patients with a limited response to this treatment, researchers report.
Data on this finding were presented March 30 at the 14th International Conference on Alzheimer’s & Parkinson’s Diseases (AD/PD 2019) in Lisbon. The research, “Variation in the L-DOPA Response in the Parkinson’s Progression Markers Initiative (PPMI) Cohort,” was part of the conference’s Symposium 52: Clinical Aspects & Therapeutic Strategies in PD.
A precise clinical diagnosis of Parkinson’s disease can be difficult in its early stages. Diagnostic criteria include the response of key motor features to levodopa (L-DOPA challenge test).
Physicians rate patient’s motor symptoms according to the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS part 3) both before and after a “single‐shot” administration of L-DOPA. If a patient’s symptoms improve while taking the medication, he or she is likely to have Parkinson’s.
However, there’s no consensus on how much the levodopa response can vary and still be considered “a response” to treatment.
Researchers at the Institute of Neuroscience and Psychology set up to quantify L-DOPA responsiveness in early Parkinson’s disease and assess its relationship with motor complications. They did so by using the Parkinson’s Progression Markers Initiative (PPMI) dataset.
PPMI was launched in 2010 by the Michael J. Fox Foundation to create a large bank of samples and data from Parkinson’s patients available to the research community. The initiative’s main goal is to identify biomarkers of Parkinson’s disease, a critical next step in the development of new and better treatments for the neurodegenerative disease.
Investigators analyzed the Movement Disorder Society (MDS)-UPDRS scores of 182 patients (69.2% men, mean age at diagnosis 62.1), before and after an L-DOPA challenge test (usual morning dose). The challenge took place 3.5 years after they were diagnosed.
An L-DOPA response of 24.5% or more was considered to be definite, while any percentage below that established threshold was taken as a limited response.
Half of the study sample had a definite levodopa response (median improvement 40.7%), while the remaining half had a limited one (median improvement 11.1%).
Around 14% of the definite L-DOPA responders had dyskinesia, which was significantly more common than in these patients than in those with a limited response (1.1% of cases).
Other motor differences were also evident between these groups: motor fluctuations were observed in 31.1% of patients with a definite response, and in 20.9% of limited responders; uncontrollable muscle contractions (dystonia) were seen in 13.3% of definite versus 5.5% of limited responders. However, differences here did not reach statistical significance.
Definite responders’ levodopa equivalent daily dose was no different than limited responders, the researchers observed.
They concluded: “Only half of early PD patients have a definite L-dopa motor response on challenge testing. Patients with a definite L-DOPA response are more likely to develop early dyskinesia than those with a limited response.”