PracticeUpdate Conference Series - ANZAN 2018

A Hyperdirect Pathway Generates Doorway Freezing in Parkinson’s Disease A hyperdirect pathway has been implicated in the generation of doorway freezing in Parkinson’s disease, reports a prospective study reported at ANZAN 2018.

S imon J.G. Lewis, MD, of the University of Sydney in Camperdown, NSW, explained that freezing of gait in Parkinson’s disease is a disabling symp- tom of advanced Parkinson’s disease and is frequently triggered on passing through narrow spaces such as doorways. Though freezing of gait is common, underlying mechanisms are poorly understood. In 2014, Dr. Lewis, Elie Matar, MBBS (also of the University of Sydney), and colleagues showed that increased footstep latency in a virtual reality envi- ronment is a surrogate measure of freezing of gait. In the present study, Dr. Lewis and coinvestigators set out to model doorway freezing utilizing the virtual reality paradigm in conjunction with functional magnetic resonance imaging (MRI) to determine neural correlates of this phenomenon. In all, 19 patients who experienced freezing of gait routinely performed a val- idated virtual reality gait paradigm where they used foot pedals to navigate a series of doorways. Patients underwent testing randomized between both on and off medication states. Task performance in conjunction with blood oxy- genation level-dependent signal changes were compared within each patient. Patients in the off state demonstrated significantly longer footstep latencies as they passed through a doorway in the virtual reality environment compared than in the on state. As seen clinically with freezing of gait, this locomotive delay was triggered pri- marily by narrow rather than wide doorways. Functional MRI analysis revealed that doorway-provoked footstep delay was associated with selective hypo- activation in the presupplementary motor area bilaterally. Task-based functional connectivity analyses showed that this delay was inversely correlated with the degree of functional connectivity between the presupplementary motor area and subthalamic nucleus across both hemispheres. Furthermore, increased frequency of prolonged footstep latency was associ- ated with increased connectivity between the bilateral subthalamic nucleus. Dr. Lewis concluded that the findings suggested that the effect of environmen- tal cues on triggering freezing of gait reflects a degree of impaired processing

Dr. Simon J.G. Lewis

Dr. Elie Matar

Dr. Victor S.C. Fung

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