Brain dysfunction in gait disorders of Caribbean atypical Parkinsonism and progressive supranuclear palsy patients: A comparative study

Abstract

Introduction: Gait disorders and falls occur early in progressive supranuclear palsy (PSP-RS) and Caribbean atypical parkinsonism (Caribbean AP). However, the link between these signs and brain lesions has never been explored in these patient populations. Here, we investigate and compare the imaging factors that relate to gait and balance disorders in Caribbean AP and PSP-RS patients.

Methods: We assessed gait and balance using clinical scales and gait recordings in 16 Caribbean AP and 15 PSP-RS patients and 17 age-matched controls. We measured the grey and white matter brain volumes on 3 T brain MRI images. We performed a principal component analysis (PCA) including all the data to determine differences and similarities between groups, and explore the relationship between gait disorders and brain volumes.

Results: Both Caribbean AP patients and PSP-RS have marked gait and balance disorders with similar severity. In both groups, gait and balance disorders were found to be most strongly related to structural changes in the lateral cerebellum, caudate nucleus, and fronto-parietal areas. In Caribbean AP patients, gait disorders were also related to additional changes in the cortex, including frontal, insular, temporal and cuneus lobes, whereas in PSP-RS patients, additional white matter changes involved the mesencephalon and parahippocampal gyrus.

Conclusion: Gait and balance disorders in Caribbean AP patients are mainly related to dysfunction of cortical brain areas involved in visuo-sensorimotor processing and self-awareness, whereas these signs mainly result from premotor-brainstem-cerebellar network dysfunction in PSP-RS patients, brain areas involved in initiation and maintenance of locomotor pattern and postural adaptation.

Keywords: Caribean atypical parkinsonism; Gait disorders; Gait recordings; Magnetic resonance imaging; Progressive supranuclear palsy.

Fig. 1

Gait initiation parameters in controls, Caribbean AP and PSP-RS patients. A) Gait initiation parameters recordings using a force platform allowing the calculation of anteroposterior (AP) and mediolateral (ML) centre of foot pressure (CoP) displacements, and anteroposterior and vertical (V) centre of gravity (CoG) velocities, and vertical displacements of right (green line) and left (red line) heels measured with the Vicon system (from left to right traces). Each trace represents the gait initiation parameters obtained during the anticipatory postural adjustments (APAs) phase and execution (EXE) of the first step in an individual control (HC, upper traces), Caribbean AP (CAP middle traces) and PSP-RS (bottom traces) patients. B) Graphs represent the gait initiation parameters obtained in controls (grey), Caribbean AP (orange) and PSP-RS (blue) patients, both in natural (N) and fast (F) gait conditions. Boxplots show the median (dark lines), interquartile (Q1-upper and Q3-bottom parts of the boxes) and range for each gait initiation parameter. t0: time of the first biomechanical event; FO1: time of the foot-off of the swing leg; FC1: foot contact of the swing leg; FO2: time of the foot-off of the stance leg; DS: double-stance phase; L: step length; W: step width; Vm: maximum AP velocity of the CoG; V1: minimum vertical velocity of the CoG and V2: vertical CoG velocity at the time of the foot-contact. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Grey and white matter volume differences in controls, Caribbean AP and PSP-RS patients. Images shows the differences between patients with Caribbean Atypical Parkinsonism (CAP), Progressive Supranuclear Palsy – Richardson’s syndrome (PSP-RS) and control subjects (C) for A) grey and B) white matter volumes. Statistical parametric maps are presented for the averaged normalized T1-wighted image of all control subjects. Voxels were considered significant at P < 0.05 and t > 3.8, false discovery rate whole brain corrected. Left is right. Scale bar indicates t-score.

Fig. 3

Multifactor analysis including clinical, gait, oculomotor and MRI data for controls, PSP-RS and Caribbean AP patients. The graphs represent the principal component analysis results for all the clinical, neurophysiological and imaging data obtained in the controls, PSPS-RS and Caribbean AP patients. This analysis discriminated the 3 groups of subjects (upper panel). Controls (blue dots) and patients are discriminated along axis 1, and Caribbean AP (red dots) and PSP-RS (green dots) patients along axis 2. The first component is mainly composed of clinical, gait and oculomotor parameters (middle panel), and the second component mainly composed of imaging, cognitive scores and gait recording parameters (bottom panel). APA = anticipatory postural adjustment, AP = anteroposterior, CoP = centre of foot pressure, DS = double-stance, ML = mediolateral, SMA = supplementary motor area, VBM = voxel-based morphometry. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Correlation analysis between brain MRI grey and white matter volumes and severity of gait and balance disorders in CAP and PSP-RS patients. A) Significant correlations found between gait and balance disorders with both clinical scales and gait recording parameters in Caribbean AP (brown and orange squares for positive and negative correlations, respectively) and PSP-RS patients (dark blue and light blue squares for positive and negative correlations, respectively). B) Visualisation of brain areas correlating with mediolateral displacement during gait initiation in Caribbean AP (upper panel) and PSP-RS (lower panel) patients. C) Graphs show the linear correlation between the GABS (upper panel) and ABC (lower panel) scales and the Magnetic Resonance Parkinsonism Index (MRPI), in both Caribbean AP and PSP-RS patients. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)