Levodopa-induced dyskinesia is associated with worse gait and balance in Parkinson's disease.

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Levodopa-induced dyskinesia (LID) is a major source of disability in advanced Parkinson's disease (PD), whose impact on gait and balance across medication states still remains unclear. We aimed to compare gait and balance performance between comparable dyskinetic (Dysk-matched) and non-dyskinetic (No-Dysk) PD patients in OFF and ON state, and to explore neural correlates using structural and resting-state functional MRI (rs-fMRI). PD patients were consecutively enrolled among candidates for device-aided therapies. Gait and balance were assessed using validated wearable inertial sensors during a 2-minute walk test, a 3-meters Timed-Up-and-Go (TUG), and a sway test, providing spatiotemporal gait parameters, variability, asymmetry, and postural sway metrics. Groups were compared using propensity score matching (PSM) for age, sex, disease duration, motor severity and axial disability. A subgroup underwent exploratory investigation with structural and rs-fMRI collected in ON state. After PSM (22 pairs), Dysk-matched group showed slower gait speed (p = 0.007), shorter stride length (p = 0.006), longer double support (p = 0.047), and prolonged TUG (p = 0.049) in the OFF state. Dysk-matched patients showed increased sway from OFF to ON (p = 0.030). Neuroimaging (10 Dysk-matched, 9 No-Dysk) revealed increased functional connectivity in sensorimotor regions and reduced SMA connectivity within a cerebellar network in Dysk-matched patients, without structural difference. Overall, the association of LID with impaired gait and postural control even in the OFF state is consistent with the hypothesis of broader motor network dysfunction beyond overt involuntary movements.

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