Abstract
Background: The widely divergent responsiveness of Parkinson’s disease (PD) patients to levodopa is an important clinical issue because of its relationship with quality of life and disease prognosis. Preliminary animal experiments have suggested that degeneration of the locus coeruleus (LC) attenuates the efficacy of levodopa treatment.Objective: To explore the relationship between LC degeneration and levodopa responsiveness in PD patients in vivo.Methods: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a good indicator of LC and substantia nigra (SN) degeneration, and levodopa challenge tests were conducted in 57 PD patients. Responsiveness to levodopa was evaluated by the rates of change of the Unified Parkinson’s Disease Rating Scale Part III score and somatomotor network synchronization calculated from resting-state functional MRI before and after levodopa administration. Next, we assessed the relationship between the contrast-to-noise ratio of LC (CNRLC) and levodopa responsiveness. Multiple linear regression analysis was conducted to rule out the potential influence of SN degeneration on levodopa responsiveness.Results: A significant positive correlation was found between CNRLC and the motor improvement after levodopa administration (R = 0.421, p = 0.004). CNRLC also correlated with improvement in somatomotor network synchronization (R = –0.323, p = 0.029). Furthermore, the relationship between CNRLC and levodopa responsiveness was independent of SN degeneration.Conclusion: LC degeneration might be an essential factor for levodopa resistance. LC evaluation using NM-MRI might be an alternative tool for predicting levodopa responsiveness and for helping to stratify patients into clinical trials aimed at improving the efficacy of levodopa.
Highlights
The widely diverse responsiveness of Parkinson’s disease (PD) patients to levodopa treatment is an important clinical issue because of its relationship with the quality of daily life and prognosis of the disease [1]
We demonstrated a significant correlation between locus coeruleus (LC) degeneration and responsiveness of PD patients to levodopa: the contrast-to-noise ratio of LC (CNRLC) correlated with the rates of change of UPDRS-III score and somatomotor network synchronization
No direct correlation was found between LC degeneration and motor disturbance, LC signal intensity in MRI scans was significantly associated with improvement of UPDRS-III score
Summary
The widely diverse responsiveness of Parkinson’s disease (PD) patients to levodopa treatment is an important clinical issue because of its relationship with the quality of daily life and prognosis of the disease [1]. The mechanisms underlying this variability of responses to treatment are unclear. Preliminary evidence from a rat PD model showed that severe LC norepinephrine deficiency reduces the efficacy of levodopa treatment [2]. The widely divergent responsiveness of Parkinson’s disease (PD) patients to levodopa is an important clinical issue because of its relationship with quality of life and disease prognosis. LC evaluation using NM-MRI might be an alternative tool for predicting levodopa responsiveness and for helping to stratify patients into clinical trials aimed at improving the efficacy of levodopa
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
