Functional analysis of supraspinal locomotor control in patients with progressive supranuclear palsy by PET

Objectives Progressive supranuclear palsy (PSP) is the most frequent atypical Parkinson syndrome, characterized by an early manifestation of gait disturbance and falls. The pathophysiology of gait dysfunction in PSP is not yet sufficiently understood. In the present study, we investigated the supraspinal locomotion network in patients with PSP during real locomotion.

Methods Twelve patients with PSP were scanned with F-18 FDG-PET during real locomotion and rest. In the locomotion paradigm subjects walked at constant velocity for 10 min. Then F-18 FDG was injected intravenously while subjects continued walking for another 10 min. Results were compared to an age-matched healthy control group (N=12).

Results The major results of this study are the following: 1) At rest, the regional cerebral glucose metabolism (rCGM) in the supraspinal locomotor centers, i.e. the prefrontal cortex, the subthalamic nucleus, the pedunculopontine/cuneiform nucleus complex, was reduced in PSP. These locomotor regions are critical for the conveyance of cortical locomotor impulses to the spinal cord. 2) Severe gait impairment, measured by gait velocity, step length and PSP rating scale/gait, was associated with decreased rCGM in the prefrontal cortex and subthalamic nucleus. 3) Accordingly during real locomotion, functional activation of the prefrontal cortex, the subthalamic nucleus, the pendunculopontine/cuneiform nucleus complex and the thalamus was reduced in PSP patients compared to controls. 4) The precentral gyrus and the vermal cerebellum were activated more strongly during locomotion in PSP patients.

Conclusions Gait impairment in PSP is especially associated with dysfunction of the indirect prefrontal-subthalamic-pedunculopontine loop of locomotor control. Simultaneously, the direct locomotor loop from the primary motor cortex including input from the cerebellar locomotor center shows increased activity in PSP patients. The latter can be interpreted as an attempt of compensation