Functional disturbance of the locomotor network in progressive supranuclear palsy
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Abstract
Objective: To determine pathologic regulations and potential compensatory mechanisms in the supraspinal locomotor network of patients with progressive supranuclear palsy (PSP) by investigation of brain activation during walking and correlation to gait performance.
Methods: Twelve patients with PSP were scanned with [18F]-FDG-PET during walking and at rest as has been described earlier. Results were compared to age-matched healthy controls (n = 12).
Results: The major results were as follows. 1) At rest, the regional cerebral glucose metabolism (rCGM) in the supraspinal locomotor centers, i.e., the prefrontal cortex, the subthalamic nucleus, and the pedunculopontine/cuneiform nucleus complex, was reduced in PSP. 2) Severity of gait impairment, measured by gait velocity, step length, and progressive supranuclear palsy rating scales/gait, correlated with decrease of rCGM in the prefrontal cortex and subthalamic nucleus. 3) Accordingly, during walking functional activation of the prefrontal cortex, the subthalamic nucleus, the pedunculopontine/cuneiform nucleus complex, and the thalamus was reduced in patients with PSP compared to controls. 4) The precentral gyrus and the vermal cerebellum were activated more strongly during locomotion in PSP.
Conclusions: Gait impairment in PSP is especially associated with dysfunction of the indirect, modulatory prefrontal–subthalamic–pedunculopontine loop of locomotor control. The direct, stereotyped locomotor loop from the primary motor cortex to the spinal cord with rhythmic cerebellar drive shows increased activity in PSP. The latter can be interpreted as an attempt of compensation, but may also contribute to a stereotyped gait pattern in PSP.
GLOSSARY
- CLR=
- cerebellar locomotor region;
- FDR=
- false discovery rate;
- MLR=
- mesencephalic locomotor region;
- PD=
- Parkinson disease;
- PSP=
- progressive supranuclear palsy;
- PSPRS=
- progressive supranuclear palsy rating scale;
- rCGM=
- regional cerebral glucose metabolism;
- ROI=
- region of interest;
- SLN=
- supraspinal locomotor network;
- SLR=
- subthalamic locomotor region
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received April 15, 2012.
- Accepted October 9, 2012.
- © 2013 American Academy of Neurology
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