Attenuation of fluctuating striatal synaptic dopamine levels in patients with Parkinson disease in response to subthalamic nucleus stimulation: a positron emission tomography study.
OBJECTIVE
The "wearing-off" phenomenon often hampers the treatment of Parkinson disease (PD). Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known to ameliorate the wearing-off phenomenon, the mechanism by which it does this remains unclear. As part of an inquiry into the mechanism of STN DBS, the authors measured synaptic dopamine levels in the striatum by performing positron emission tomography (PET) with [11C]raclopride.


METHODS
Three patients with PD who were experiencing the wearing-off phenomenon underwent PET scanning before and after DBS of the STN. The clinical features in these patients were evaluated by applying the Hoehn and Yahr, United Parkinson's Disease Rating, and Schwab and England Activities of Daily Living Scales. Before and after surgery, PET scans were obtained using [11C]raclopride prior to and 1 hour following an oral administration of levodopa. Regions of interest for the [11C]raclopride binding potential (RacloBP) were set in the bilateral putamen and the caudate nucleus. All clinical scores were dramatically improved postoperatively. Deep brain stimulation of the STN reduced the baseline RacloBP in both the putamen and caudate nucleus, but the differences between the pre- and postoperative levels were insignificant. Before DBS of the STN, the levodopa administration significantly reduced RacloBP in the putamen (p < 0.0001). Postoperatively the drug-induced reduction in RacloBP became statistically insignificant. The drug-induced increase in synaptic dopamine concentrations in the putamen preoperatively was estimated to be approximately four times higher than that after surgery (p < 0.01). The drug-induced RacloBP change in the caudate nucleus was similar to that in the putamen, although the magnitude of the change was lower (p < 0.005). The drug-induced increase in the caudate nucleus was also reduced postoperatively (p < 0.05).


CONCLUSIONS
Deep brain stimulation of the STN induces the stabilization of synaptic dopamine concentrations in the striatum and may attribute to the alleviation of levodopa-related motor fluctuations.
Nimura
Taro
T
Department of Neurosurgery, Miyagi National Hospital, Japan. nimurat@mac.com
Yamaguchi
Keiichiro
K
Ando
Tadashi
T
Shibuya
Satoshi
S
Oikawa
Takanori
T
Nakagawa
Atsuhiro
A
Shirane
Reizo
R
Itoh
Masatoshi
M
Tominaga
Teiji
T
D000368:Aged; D002421:Caudate Nucleus / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D046690:Deep Brain Stimulation; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000378:metabolism; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000378:metabolism; D020891:Raclopride / Q000378:metabolism; D012720:Severity of Illness Index; D013238:Stereotaxic Techniques; D020531:Subthalamic Nucleus / Q000503:physiopathology*; D016896:Treatment Outcome
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D020891:Raclopride; D007980:Levodopa; D004298:Dopamine