White Matter Hyperintensities May Increase Risk of Levodopa-Induced Dyskinesia in Parkinson Disease

Han Soo Yoo, MD

New study results suggest that the burden of white matter hyperintensities is associated with risk of developing levodopa-induced dyskinesia (LID) in patients with Parkinson disease (PD).

The study included 336 patients with drug-naïve early stage PD who were treated PD medication for at least 3 years to assess the association between WMH and the risk of LID in patients with PD.

Brian magnetic resonance imaging (MRI) scans, including fluid‐attenuated inversion recovery (FLAIR) sequence images, and ¹⁸F‐N‐(3‐fluoropropyl)‐2β‐carbon ethoxy‐3β‐(4‐iodophenyl) nortropane (¹⁸F‐FP‐CIT) positron emission tomography (PET), were completed upon initial assessment. Each patient was rated on FLAIR images using the Clinical Research Center for Dementia of South Korea (CREDOS) WMH visual rating scale.

Ultimately, 227 patients were classified as having minimal WMHs and 109 were classified as having moderate to severe WMHs. Notably, those with moderate to severe WMH were older, had higher scores on the Unified Parkinson’s Disease Rating Scale-3, and were more likely to have hypertension and diabetes.

Investigators rated periventricular and lobar (frontal, parietal, temporal, and occipital) WMHs, as well as separately rating basal ganglia and infratentorial signal hyperintensities.

Cox regression analysis was used to assess the regional WMH burden on the development of LID, with adjustments for age at PD onset, sex, dopamine transporter availability in the posterior putamen, and levodopa-equivalent doses per body weight.

Results from the Kaplan-Meier analysis showed that those with moderate to severe WMHs had a greater risk of developing LID than those with minimal WMHs (P_l < .001). When the model was adjusted for age at PD onset, sex, baseline striatal dopamine depletion, and levodopa-equivalent doses per body weight, the hazard ratio (HR) for developing LID after initiation of PD medication in the moderate to severe group compared with the minimal group was 2.660 (95% CI, 1.742-4.062; P <.001).

Data from the Cox regression model showed a correlation between greater WMH burden and greater risk of developing LID in either overall samples (HR 1.044; 95% CI, 1.018-1.071; P = .001) and propensity score subsamples (HR 1.040; 95% CI, 1.012—1.069; P = .005).

“Based on previous and current studies, the WMH burden seems to be an important clinical parameter, acting as a predictor of parkinsonian motor outcome, as well as LID development in patients with PD,” the study authors wrote. “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.”

REFERENCE

Chung SJ, Yoo HS, Lee YH, et al. White matter hyperintensities and risk of levodopa-induced dyskinesia in Parkinson’s disease. Ann Clin Transl Neurol. Published online February 7, 2020. doi: 10.1002/acn3.50991.