Pharmacological treatment in Parkinson's disease: Effects on gait

Abstract

Gait impairments are a hallmark of Parkinson's disease (PD), both as early symptom and an important cause of disability later in the disease course. Although levodopa has been shown to improve gait speed and step length, the effect of dopamine replacement therapy on other aspects of gait is less well understood. In fact, falls are not reduced and some aspects of postural instability during gait are unresponsive to dopaminergic treatment. Moreover, many medications other than dopaminergic agents, can benefit or impair gait in people with PD. We review the effects of pharmacological interventions used in PD on gait, discriminating, whenever possible, among effects on four components of everyday mobility: straight walking, gait initiation, turning, gait adaptability. Additionally, we summarize the effects on freezing of gait. There is substantial evidence for improvement of spatial characteristics of simple, straight-ahead gait with levodopa and levodopa-enhancing drugs. Recent work suggests that drugs aiming to enhance the acetylcholine system might improve gait stability measures. There is a lack of well-designed studies to evaluate effects on more complex, but highly relevant walking abilities such as turning and making flexible adjustments to gait. Finally, paucity in the literature exists on detrimental effects of drugs used in PD that are known to worsen gait and postural stability in the elderly population.

Keywords: Acetylcholine; Dopamine; Falls; Gait; Turning.

Figure 1

Different components of walking in everyday life and related objective outcome measures. A. Straight walking can be characterized by spatial and temporal variables of the stride (left-left heel strike) and step (left-right heel strike), motion of the arm and trunk, and gait speed and cadence (steps per minute). Stability of gait can be indicated by step-to-step or stride-to-stride (depicted here) variability of stride length. Low variability indicates that the stride length or stride time is relatively constant, whereas high variability indicates large changes of stride length or stride time between strides. Double support time is defined as the percentage of the gait cycle during which both feet are in contact with the ground; i.e. between heel strike of one foot and toe-off of the other foot. B. Gait initiation can be characterized by the anticipatory postural adjustment (APA) that precedes the onset of the first step. The CoP first moves posteriorly and toward the stepping foot in order to accelerate the CoM forward and toward the stance foot. Execution of the first step is described in terms of step length and step duration. C. Turning during walking consists of a sequence of rotations of eyes-head-trunk-feet. The turning velocity and duration are most commonly quantified using the trunk motion. Finally number of steps needed to complete the turn is a common outcome measure. D. Gait adaptability, here limited to obstacle avoidance, can be quantified as the ability to prevent collision with the obstacle, the clearance of the crossing foot, foot placement, time spent on one leg and total duration of obstacle crossing. Stability during obstacle crossing can be measured by quantifying CoM movement. * Variables that are not affected in PD as compared to their healthy peers. Abbreviations: CoP: center of pressure; CoM: center of mass.

Figure 2

A summary of the relative effects of taking levodopa on a wide variety of gait parameters during straight walking, gait initiation, and turning in a study of 100 people with PD. This study is an example of how upper and lower body bradykinetic aspects of gait improve with levodopa, whereas measures related to stability of gait (such as double support time) did not. The standardized response mean reflects the size of the improvement with levodopa and is calculated as the mean score change divided by the standard deviation of the score change. Adapted from C. Curtze, J.G. Nutt, P. Carlson-Kuhta, M. Mancini, F.B. Horak, Levodopa Is a Double-Edged Sword for Balance and Gait in People With Parkinson's Disease, Mov Disord (2015). Copyright 2015 by the John Wiley & Sons, Inc. Adapted with permission.