April 2011
Ahmed I, Bose SK, Pavese N, Ramlackhansingh A, Turkheimer F, Hotton G,
Hammers A, Brooks DJ
Levodopa-induced dyskinesias are a common complication of long-term
therapy in Parkinson’s disease. Although both pre- and
post-synaptic mechanisms seem to be implicated in
their development, the precise physiopathology of these disabling
involuntary
movements remains to be fully elucidated.
Abnormalities in glutamate transmission (over expression and
phosphorylation of
N-methyl-d-aspartate
receptors) have been associated with the development of
levodopa-induced dyskinesias in animal models of Parkinsonism.
The role of glutamate function in dyskinetic
patients with Parkinson’s disease, however, is unclear.
We used 11C-CNS 5161 [N-methyl-3(thyomethylphenyl)cyanamide] positron emission tomography, a marker of activated N-methyl-d-aspartate receptor ion channels, to compare in vivo
glutamate function in parkinsonian patients with and without
levodopa-induced dyskinesias. Each patient was assessed with
positron emission tomography twice, after taking
and withdrawal from levodopa. Striatal and cortical tracer uptake was
calculated
using a region of interest approach.
In the ‘OFF’
state withdrawn from levodopa, dyskinetic and non-dyskinetic patients
had
similar levels of tracer uptake in basal ganglia
and motor cortex. However, when positron emission tomography was
performed
in the ‘ON’ condition, dyskinetic patients had
higher 11C-CNS 5161 uptake in caudate, putamen and precentral
gyrus compared to the patients without dyskinesias, suggesting that
dyskinetic
patients may have abnormal glutamatergic
transmission in motor areas following levodopa administration.
These
findings are
consistent with the results of animal model studies
indicating that increased glutamatergic activity is implicated in the
development and maintenance of levodopa-induced
dyskinesias. They support the hypothesis that blockade of glutamate
transmission
may have a place in the management of disabling
dyskinesias in Parkinson’s disease.
