Pavese N, Evans A H, Tai Y F, Hotton G, Brooks D J, Lees A J, Piccini P
MRC Clinical Sciences Centre and Division of Neurosciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
Neurology. 2006 Nov 14;67(9):1612-7. doi: 10.1212/01.wnl.0000242888.30755.5d.
To evaluate the relationship between clinical improvement and in vivo synaptic dopamine (DA) release after a single oral dose of levodopa (LD) in patients with advanced Parkinson disease (PD).
We studied 16 patients with advanced PD with [(11)C]raclopride (RAC) PET. Each patient had RAC PET twice: once when medication had been withdrawn and once after an LD challenge. On the day of the LD challenge scan, oral 250 mg LD/25 mg carbidopa was given before scanning. Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were rated in an "off" state before LD and again at the end of PET.
All the patients were still in "on" state at the end of their LD challenge RAC PET scans. Following LD, mean caudate and putamen RAC binding potentials (BPs) were significantly lower vs baseline, consistent with increased synaptic DA. Individual LD-induced improvements in UPDRS score correlated significantly with reductions in putaminal BP. Additionally, large putaminal RAC BP changes were associated with higher dyskinesia scores. When motor UPDRS subitems were examined, improvements in rigidity and bradykinesia, but not in tremor or axial symptoms, correlated with putamen DA release.
In advanced Parkinson disease, the improvement of rigidity and bradykinesia and the presence of dyskinesias after a single dose of oral levodopa are governed by the level of dopamine generated at striatal D2 receptors. In contrast, relief of parkinsonian tremor and axial symptoms is not related to striatal synaptic dopamine levels and presumably occurs via extrastriatal mechanisms.
评估晚期帕金森病（PD）患者单次口服左旋多巴（LD）后临床改善情况与体内突触多巴胺（DA）释放之间的关系。
我们对16例晚期PD患者进行了[（11）C]雷氯必利（RAC）正电子发射断层扫描（PET）研究。每位患者进行两次RAC PET检查：一次在停药时，一次在LD激发试验后。在进行LD激发试验扫描当天，扫描前口服250 mg LD/25 mg卡比多巴。在LD给药前的“关”状态下以及PET检查结束时，对统一帕金森病评定量表（UPDRS）运动评分进行评定。
所有患者在LD激发试验RAC PET扫描结束时仍处于“开”状态。服用LD后，尾状核和壳核的平均RAC结合电位（BP）较基线显著降低，这与突触DA增加一致。LD引起的UPDRS评分个体改善与壳核BP降低显著相关。此外，壳核RAC BP的大幅变化与较高的异动症评分相关。当检查运动UPDRS子项目时，强直和运动迟缓的改善与壳核DA释放相关，而震颤或轴性症状的改善则与之无关。
在晚期帕金森病中，单次口服左旋多巴后强直和运动迟缓的改善以及异动症的出现受纹状体D2受体处产生的多巴胺水平支配。相比之下，帕金森震颤和轴性症状的缓解与纹状体突触多巴胺水平无关，可能是通过纹状体以外的机制发生的。
