Objective: To characterize motor fluctuations and dyskinesias in patients with LRRK2-associated Parkinson’s disease.

Background: Motor complications, including dyskinesias and motor fluctuations, are hallmarks of advanced Parkinson’s disease, but their profile in G2019S LRRK2 carriers is incompletely described.

Method: We conducted a retrospective study of patients with Parkinson’s disease carrying the LRRK2 G2019S mutation who developed motor fluctuations and/or dyskinesias. Demographic, genetic, clinical, and therapeutic data were collected. Multivariate linear regression was used to identify factors associated with delays to dyskinesia and motor fluctuation onset.

Results: A total of 136 patients were included (73 men, 53.7%). Genetic status was heterozygous in 92.1% and homozygous in 7.9% of carriers of the LRRK2 G2019S mutation. Mean age at disease onset was 53.3 ± 11.6 years (range 22–84). Mean disease duration at evaluation was 9.4 ± 5.9 years among the 114 patients with available UPDRS Part IV data. The mean MDS-UPDRS Part IV total score was 6.76 ± 4.13 (range 0–18; n = 112).

The mean delay from disease onset to dyskinesia was 8.5 ± 4.4 years (range 1.5–20) in 77 patients, while the mean delay to motor fluctuations was 5.8 ± 2.9 years (range 1–17) in 133 patients.

In multivariate linear regression for dyskinesia onset, the model had limited explanatory power (R² = 0.156). Delay of levodopa introduction was independently associated with dyskinesia onset (β = 0.336, p = 0.015), whereas genotype (β = −0.150, p = 0.275), age at onset (β = −0.059, p = 0.661), and sex (β = 0.058, p = 0.663) were not significant.

For motor fluctuations, the model explained variability in onset (adjusted R² = 0.174). Delay of levodopa initiation was the only independent predictor (β = 0.451, p < 0.001), while age at onset (β = −0.036, p = 0.723), sex (β = 0.033, p = 0.774), and genotype (β = 0.043, p = 0.663) were not significant.

Conclusion: In LRRK2-associated Parkinson’s disease, motor complications showed substantial inter-patient variability, highlighting clinical heterogeneity. Earlier levodopa initiation was independently associated with the onset of both dyskinesias and motor fluctuations, whereas age, sex, and genotype were not significant predictors.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-fluctuations-and-dyskinesias-in-lrrk2-associated-parkinsons-disease/