A pathophysiological model of freezing of gait in Parkinson's disease

Abstract

Freezing of gait (FOG) is a common phenomenon in Parkinson's disease (PD) affecting over half of those in the advanced stages of the disease and often does not respond to standard drug therapies. This article proposes a possible mechanism by which this disorder of movement comes about. Co-ordinated neural activities are dependent on a series of parallel neuronal networks passing through the basal ganglia connecting and integrating functions. In healthy subjects, these competing, yet complementary, networks permit tight regulation in the broad domains of motor, cognitive, and limbic functions. In patients with PD, the loss of striatal dopamine coupled with the limited repertoire of the output nuclei within these pathways allows for an element of 'cross-talk' between competing inputs, which in turn could lead to a paroxysmal excessive inhibition of the thalamus and pedunculopontine nucleus triggering freezing of gait. It is further postulated that this phenomenon may be acting via a transient period of increased synchronization within the basal ganglia oscillations.