Functional disturbance of the locomotor network in progressive supranuclear palsy.
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.
Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, Germany. andreas.zwergal@med.uni-muenchen.de
Andreas
A
Zwergal
Christian
C
la Fougère
Stefan
S
Lorenzl
Axel
A
Rominger
Guoming
G
Xiong
Lorenz
L
Deutschenbaur
Florian
F
Schöberl
Jennifer
J
Linn
Marianne
M
Dieterich
Thomas
T
Brandt
Michael
M
Strupp
Peter
P
Bartenstein
Klaus
K
Jahn
D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008124:Locomotion / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies; D012146:Rest; D012720:Severity of Illness Index; D013494:Supranuclear Palsy, Progressive / Q000473:pathology* / Q000503:physiopathology*
D019788:Fluorodeoxyglucose F18