These findings suggest that baseline white matter hyperintensities can act as a predictive marker or therapeutic target for the development of levodopa-induced dyskinesia in patients with early stage Parkinson disease.
In patients with Parkinson disease (PD) the burden of white matter hyperintensities (WMHs) is associated with occurrence of levodopa-induced dyskinesia (LID), suggesting that comorbid WMHs may be a risk factor for LID, according to a recent study.
The research, published in the Annals of Clinical and Translational Neurology, used the Clinical Research Center for Dementia of South Korea WMH visual rating scale to divide 336 patients with drug-naïve early stages PD into 2 groups: minimal WMHs (PD-WMH-) and moderate-to-severe WMHs (PD-WMH+). The study then estimated the hazard ratio for the development of LID in each group and adjusted for age at PD onset, sex, striatal dopamine depletion, and PD medication dose.
“The pathogenesis underlying LID consists of 2 major events: loss of nigral dopaminergic neurons with an impaired capacity for striatal dopamine storage and plastic alterations of the basal ganglia structures in response to pulsatile stimulations with exogenous dopamine,” noted the authors. “Additionally, it has been widely gaining acceptance that both presynaptic and postsynaptic mechanisms are likely to result in aberrant plasticity in motor networks (i.e., striato‐cortical, cortico‐cortical, and cerebello‐cortical connections), which is also associated with the early development of LID.
The results revealed that those in the PD-WMH+ group were older and had more severe motor signs associated with PD despite comparable striatal dopamine transporter availability than those in the PD-WMH- group. Additionally, the study found that the PD-WMH+ group had a greater risk of developing LID than those in the PD-WMH- group, after adjusting for other factors.
“This study investigated the effects of baseline WMH burden on the development of LID in patients with drug‐naïve early stage PD. These findings suggest that baseline WMHs can act as a predictive marker or therapeutic target for the development of LID in patients with early stage PD,” noted the authors. “In conclusion, this study demonstrates that the burden of WMHs is associated with the occurrence of LID in patients with PD. These findings suggest that comorbid WMHs may affect the subcortical motor pathways, leading to an increased risk of developing LID.”
The researchers concluded that there was a greater WMH burden with earlier occurrence of LID, although the effects of WMHs on LID development did not demonstrate patterns in specific regions.
Chung SJ, Yoo HS, Lee YH, et al. White matter hyperintensities and risk of levodopa‐induced dyskinesia in Parkinson’s disease [published online February 7, 2020]. Ann Clin Transl Neurol https://doi.org/10.1002/acn3.50991