Reduced Short-Latency Afferent Inhibition in Parkinson's Disease Patients with L-dopa-Unresponsive Freezing of Gait.

BACKGROUND

Freezing of gait (FOG) in Parkinson's disease (PD), especially the "L-dopa-unresponsive" subtype, is associated with the dysfunction of non-dopaminergic circuits.

OBJECTIVE

We sought to determine whether cortical sensorimotor inhibition evaluated by short-latency afferent inhibition (SAI) related to cholinergic and gamma-aminobutyric acid (GABA)-ergic activities is impaired in PD patients with L-dopa-unresponsive FOG (ONOFF-FOG).

METHODS

SAI protocol was performed in 28 PD patients with ONOFF-FOG, 15 PD patients with "off" FOG (OFF-FOG), and 25 PD patients without FOG during medication "on" state. Additionally, 10 ONOFF-FOG patients underwent SAI testing during both "off" and "on" states. Twenty healthy controls participated in this study. Gait was measured objectively using a portable Inertial Measurement Unit system, and participants performed 5-meter Timed Up and Go single- and dual-task conditions. Spatiotemporal gait characteristics and their variability were determined. FOG manifestations and cognition were assessed with clinical scales.

RESULTS

Compared to controls, PD patients without FOG and with OFF-FOG, ONOFF-FOG PD patients showed significantly reduced SAI. Further, dopaminergic therapy had no remarkable effect on this SAI alterations in ONOFF-FOG. Meanwhile, OFF-FOG patients presented decreased SAI only relative to controls. PD patients with ONOFF-FOG exhibited decreased gait speed, stride length, and increased gait variability relative to PD patients without FOG and controls under both walking conditions. For ONOFF-FOG patients, significant associations were found between SAI and FOG severity, gait characteristics and variability.

CONCLUSION

Reduced SAI was associated with severe FOG manifestations, impaired gait characteristics and variability in PD patients with ONOFF-FOG, suggesting the impaired thalamocortical cholinergic-GABAergic SAI pathways underlying ONOFF-FOG.