Re-examining the pathobiological basis of gait dysfunction in Parkinson's disease

Abstract

Parkinson's disease (PD) is a significant source of morbidity, especially with an aging population. Gait problems, particularly freezing of gait (FOG), remain a persistent issue, causing falls and reduced quality of life without consistent responses to therapies. PD and related symptoms have classically been attributed to dopamine deficiency secondary to substantia nigra degeneration from Lewy body (LB) and Lewy neurite (LN) infiltration. However, Lewy-related pathology is present in other areas of the brainstem and spinal cord that control gait function, yet these other circuits have not been routinely considered in the design of current therapeutic options. In this review, we summarize changes in brainstem and spinal cord circuits in individuals affected by PD and the implications for understanding of gait dysfunction in PD.

Keywords: Lewy body; brainstem; circuit; freezing; movement disorder; spinal cord.