Freezing-related perception deficits of asymmetrical walking in Parkinson's disease.

Patients with Parkinson's disease (PD), and especially those with freezing of gait (FOG), are known to experience impairments in gait rhythmicity, symmetry, and bilateral coordination between both legs. In the current study, we investigated whether deficits in perception of gait speed between limbs were more pronounced in freezers than in non-freezers and could explain some of these gait impairments. We also assessed cognitive ability and proprioception. Twenty-five PD patients (13 freezers, 12 non-freezers) and 12 healthy controls walked on a split-belt treadmill, while the speed of one of the belts was gradually increased. Participants had to indicate the moment at which they perceived belt speeds to be different. The main outcome variables were the number of correct responses (perception accuracy) and the difference in belt speeds at the moment the participants perceived belt speeds to be different (perception threshold). In addition, gait characteristics during both split- and tied-belt walking were determined. Results showed significantly lower perception accuracy in freezers, whereas the perception threshold did not differ between groups. During tied-belt walking, freezers exhibited more asymmetrical step lengths and limb excursions than non-freezers and healthy controls. Greater step length and limb excursions were associated with better perception, whereas more variable gait was associated with more impaired perception. The results confirm the hypothesis that freezers have impaired perception of locomotor asymmetry. While proprioceptive and cognitive ability did not explain these findings, the possible causal link with the occurrence of FOG needs further corroboration.

Progression of postural control and gait deficits in Parkinson's disease and freezing of gait: A longitudinal study.

BACKGROUND AND AIMS: The relationship between impaired postural control and freezing of gait (FOG) in Parkinson's disease (PD) is still unclear. Our aim was to identify if postural control deficits and gait dysfunction progress differently in freezers compared to non-freezers and whether this relates to FOG development. METHODS: 76 PD patients, classified as freezer (n = 17) or non-freezer (n = 59), and 24 controls underwent a gait and postural control assessments at baseline and after 12 months follow-up. Non-freezers who developed FOG during the study period were categorized as FOG converters (n = 5). Gait was analyzed during walking at self-preferred pace. Postural control was assessed using the Mini-BESTest and its sub-categories: sensory orientation, anticipatory, reactive and dynamic postural control. RESULTS: Mini-BESTest scores were lower in PD compared to controls (p < 0.001), and in freezers compared to non-freezers (p = 0.02). PD has worse anticipatory (p = 0.01), reactive (p = 0.02) and dynamic postural control (p = 0.003) compared to controls. Freezers scored lower on dynamic postural control compared to non-freezers (p = 0.02). There were no baseline differences between converters and non-converters. Decline in postural control was worse in PD compared to controls (p = 0.02) as shown by a greater decrease in the total Mini-BESTest score. Similar patterns were found in freezers (p = 0.006), who also showed more decline in anticipatory (p < 0.001) and dynamic postural control (p = 0.02) compared to non-freezers. FOG converters had a greater decline in the total Mini-BESTest (p = 0.005) and dynamic postural control scores (p = 0.04) compared to non-converters. Gait outcomes showed no significant differences in any of the analyses. CONCLUSION: FOG is associated with more severe decline in postural control, which can be detected by the clinical Mini-BESTest.

Functional connectivity alterations in the motor and fronto-parietal network relate to behavioral heterogeneity in Parkinson's disease.

BACKGROUND: Insight into the neural mechanisms of postural instability and gait disorder (PIGD) and tremor dominant (TD) subtypes in Parkinson's disease (PD) is indispensable for generating pathophysiology hypotheses underlying this phenotyping. This cross-sectional study aimed to gain insight in specific and brain-wide functional connectivity (FC) and its correlation with motor deterioration and preservation in PD subtypes. METHODS: 68 PD patients classified as PIGD (n = 41), TD (n = 19) or indeterminate (n = 8) and 19 age-matched controls underwent resting-state fMRI while 'off' medication to assess FC between regions of interest (ROIs) in the motor and fronto-parietal network and on a whole-brain level using a parcellated template. FC alterations were correlated with quantitative behavioral measures. RESULTS: ROI-analyses showed decreased FC between the caudate and putamen in PIGD compared to TD. This hypo-connectivity was correlated with behavioral impairment. In contrast, TD-specific hyper-connectivity between motor cortical areas and the inferior parietal lobule correlated with less behavioral impairment, suggesting compensatory mechanisms. Both subgroups showed hyper-connectivity between the left supplementary motor area and pedunculopontine nucleus, whereas PIGD-specific right lateralized hyper-connectivity was shown between this nucleus and the premotor cortex. Whole-brain analyses revealed 65% hypo-connectivity and 35% hyper-connectivity in PIGD compared to TD. TD also revealed primarily hypo-connectivity compared to controls, but had more pronounced hyper-connectivity involving temporo-occipital areas. CONCLUSION: This multilevel analysis showed differential connectivity alterations in large scale neural networks and between motor and cognitive control areas that related to behavioral heterogeneity in PD, underscoring the classic TD-PIGD phenotypical classification.

Distal motor deficit contributions to postural instability and gait disorder in Parkinson's disease.

Clinical subtypes in Parkinson's disease (PD) are often based on the presence of clustered motor symptoms. In contrast to the tremor dominant (TD) subtype, the postural instability and gait disorder (PIGD) subtype is characterized by predominantly axial motor involvement and increased cognitive impairment. It is, however, unclear if subtypes represent distinct underlying neuropathological mechanisms or reflect more severe disease progression. We aimed to clarify the validity of PD subtypes by investigating behavioral outcomes at multiple levels. Therefore, spatiotemporal kinematics of gait, upper and lower limb repetitive movements in combination with a balance and cognitive assessment were recorded in 73 patients with PD. We classified patients as PIGD (n=43), TD (n=22) or indeterminate (n=8) while 'off' medication and recruited 20 age-matched controls. Surprisingly, differences between PIGD and TD were more prominent during repetitive distal motor tasks than during gait. Gait impairment in PIGD was only shown by reduced step length and gait speed. However, motor scaling and coordination of distal movements were more affected in PIGD than in TD patients. PIGD patients also had impaired postural control compared to TD patients as shown by lower mini-BESTest scores. There were no cognitive differences between patient subgroups. Distal movement was not significantly different in TD patients from controls, except for greater movement asymmetry. The results indicate a widespread impairment within PIGD with more pronounced distal than axial motor deficits. This suggests involvement of different neurotransmitter systems in the neuropathology of PD subtypes, which are at least partially independent of disease progression.