Axial kinesthesia is impaired in Parkinson's disease: effects of levodopa

Abstract

Integration of sensory and motor inputs has been shown to be impaired in appendicular muscles and joints of Parkinson's disease (PD) patients. As PD advances, axial symptoms such as gait and balance impairments appear, which often progresses to complete inability stand or walk unaided. The current study evaluates kinesthesia in the axial musculature of PD patients during active postural control to determine whether impairments similar to those found in the appendages are also present in the hip and trunk. Using axial twisting, we quantified the detection threshold and directional accuracy of the hip relative to the feet (i.e. Hip Kinesthesia) and the hip relative to the shoulders (i.e. Trunk Kinesthesia). The relation of kinesthetic threshold to disease progression as measured by UPDRS and the effect of levodopa treatment on kinesthesia were assessed in 12 PD compared to age-matched controls. Subjects stood unaided while passively twisted at a very low constant rotational velocity (1 degrees /s). The results showed that accuracy in determining the direction of axial twisting was reduced in PD relative to healthy control subjects in the hip (PD-ON: 81%; PD-OFF: 91%; CTL=96%) and trunk (PD-ON: 81%; PD-OFF: 88%; CTL=95%). Thresholds for perception of axial twisting were increased when PD subjects were ON levodopa versus OFF in both the hip (p<0.01) and the trunk (p<0.05). The magnitude of decrease in sensitivity due to being ON levodopa was significantly correlated with the increase in UPDRS motor scores (Hip: r=0.90, p<0.01 and Trunk: r=0.60, p<0.05). This effect was not significantly correlated with equivalent levodopa dosage. PD subjects with disease onset on the left side of their body showed significantly higher axial thresholds than subjects with right PD onset (p<0.05). In conclusion, deficits in axial kinesthesia seem to contribute to the functional impairments of posture and locomotion in PD. Although levodopa has been shown to improve appendicular kinesthesia, we observed the opposite in the body axis. These findings underscore the dissociable neurophysiological circuits and dopaminergic pathways that are known to innervate these functionally distinct muscle groups.

Copyright 2010 Elsevier Inc. All rights reserved.

Figures

Fig. 1

Left – In the Hip Kinesthesia condition, the torsional platform rotates (white arrow arc) the feet relative to the pelvis that is fixed against rotation by a double-hinge to allow for normal sway excursions and provide no postural support. Right – In the Trunk Kinesthesia condition, the platform rotates (white arrow arc) the feet and pelvis together relative to the upper trunk. The pelvis is fixed to the rotating support surface by a single-hinge allowing anterior-posterior sway, while the shoulder girdle is fixed against rotation by a double-hinge to a fixation frame. Both the Trunk and Hip configurations require active postural control and provide no support. The subject held a bi-directional button with both hands at waist-height (not pictured).

Fig. 2

The proprioceptive stimulus and directional button-push response show how threshold and direction are measured. Axial rotation (thin line) is 10° CC/Left (up) or CW/Right (down) at 1°/s. a) The four directions with pauses in between (separated by vertical dotted lines) are CC from 0° to 10°L, CW from 10°L to 0°, CW from 0° to 10°R, or CC from 10°R to 0°, where 0° is considered a neutral, untwisted bodily configuration. Voltage signals (thick vertical spikes) show directional button-push response (CC=up, CW=down). The CW directional spike in the bottom left corner depicts a MISS, whereas all other spikes depict HITS. b) An expanded view of CC 0-10L, pause, CW 10L-0 test phases. If the response (thick line) occurs 5.4 seconds after platform rotation onset (dotted line), then the amount of axial rotation equals 5.4°, which is the kinesthetic threshold for that trial. An upward voltage spike indicates the subject perceived CC axial rotation and a downward voltage spike indicates the perception of CW axial rotation. To avoid more than 10° of axial abduction, CW 0-10L was always followed by CC 10L-0 and CC 0-10R was followed by CW 10R-0, however adduction from 10° to 0° could be followed by either CW 0-10R or CC 0-10L.

Fig. 3

Accuracy of perceiving the direction of axial rotation and threshold of detecting the onset of axial rotation. a) The average percentage of accurate responses for PD subjects ON (black bar) or OFF (gray bar) medication, and age-matched control (white bar) show a significant difference (*, p

Fig. 4

Asymmetries in PD with left (LPD) versus right (RPD) disease onset. a) LPD have higher axial kinesthetic thresholds than RPD in both the trunk and hip (p

Fig. 5

Levodopa induced changes in threshold when ON versus OFF are positively correlated with disease severity (UPDRS scores when OFF-meds), axial symptoms (Axial-UPDRS scores OFF meds), and postural instability and gait disturbance (PIGD-UPDRS scores OFF meds). A positive value for “ON minus OFF” (y-axis) indicates that the threshold increased when ON-meds, i.e. sensitivity decreased when ON-meds. (Top row) a) Disease severity (r=0.90, p