By Lucy Piper, Senior medwireNews
Reporter
Increased serotonergic fibre
innervation relative to dopaminergic fibre availability may be a potential
marker of disease progression in Parkinson’s disease (PD) patients and a
possible warning of levodopa-induced dyskinesia (LID), indicates an in vivo
imaging study.
The researchers found that
serotonergic innervation relative to dopamine fibre availability increased in
the putamen of 30 patients with the condition in line with clinical PD
progression and was highest in 10 of the patients with established dyskinesia.
“[Serotonergic] fibres have the
potential to convert [levodopa] into dopamine; thus, in advanced PD where
substantial dopaminergic fiber degeneration occurs, these fibers may be a major
source of dopamine release in the basal ganglia”, explains the team in Neurology.
This makes blocking the
serotonergic fibres as a means of reducing LID unhelpful because it could
reduce the antiparkinsonian benefit of levodopa.
But, in a related editorial,
Philippe Huot (University of Montreal, Quebec, Canada) and William Hutchison
(University of Toronto, Ontario, Canada) say the current findings could
“provide a way to determine when dyskinesia will begin at the clinical level”.
The threshold at which dopamine
release by serotonin fibres is greater than the dopamine released by the
remaining dopaminergic fibres represents a “tipping point” beyond which
dyskinesia is likely to be present, below this, as yet to be determined,
threshold, dyskinesia will be absent, they comment.
So by monitoring the putaminal
ratio of serotonin to dopamine transporters, “it might be possible to begin
administering agents that could delay, or even prevent, the emergence of dyskinesia,
were such agents to exist and be clinically available”, the editorialists
suggest.
Researchers Jee-Young Lee (Seoul
National University, South Korea) and colleagues measured the binding
potentials of dopamine and serotonin using positron emission tomography scans
with the two tracers 18F-FP-CIT and 11C-DASB, respectively.
18F-FP-CIT showed significant
functional loss of nerve terminals expressing dopamine transporters (DAT) in
the caudate, putamen and globus pallidus of the 30 patients, being worse for
the 20 patients who had received levodopa treatment, irrespective of dyskinesia
status, relative to the 10 patients in the early stages of PD who were
treatment naïve.
11C-DASB showed that nerve
terminals expressing serotonin transporters (SERT) were significantly decreased
in the caudate and putamen in the 10 PD patients who had received levodopa and
developed dyskinesia compared with the treated PD patients without dyskinesia
and non-treated PD patients.
While both tracer uptakes decreased
with PD progression, they showed topographical differences, in that DAT binding
loss correlated with severity and duration of PD for both the caudate and
putamen, but only for the caudate in the case of SERT binding loss.
The researchers looked at the ratio
of serotonin to dopaminergic fibre availability and found that it was highest
in the putamen of PD patients with dyskinesia, reaching an average of 0.78. The
ratio was lowest for treatment-naïve PD patients and intermediate for treated patients
without dyskinesia.
The ratio of serotonin to
dopaminergic fibre availability at the putamen correlated positively with
Unified Parkinson’s Disease Rating Scale (UPDRS) total scores and duration of
PD, while pallidal binding ratio additionally correlated with the UPDRS motor
scores but did not differ significantly between patients with and without
dyskinesia.
The researchers therefore conclude:
“Relative increases in the availability of serotonergic fibers compared with
dopaminergic fibers might be a predictor of future risk of dyskinesia and might
be a more sensitive marker of disease severity than clinical variables such as
disease duration or UPDRS score.”
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http://www.news-medical.net/news/20150817/Putaminal-serotonergic-innervation-flags-levodopa-induced-dyskinesia-risk.aspx
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