Karimi M, Golchin N, Tabbal S D, Hershey T, Videen T O, Wu J, Usche J W M, Revilla F J, Hartlein J M, Wernle A R, Mink J W, Perlmutter J S
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Brain. 2008 Oct;131(Pt 10):2710-9. doi: 10.1093/brain/awn179. Epub 2008 Aug 12.
Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.
丘脑底核深部脑刺激（STN DBS）可改善特发性帕金森病的运动症状，但其作用机制仍不清楚。先前的研究表明，STN DBS可增加其直接下游靶点的局部脑血流量（rCBF），但未揭示哪些脑区可能存在与运动表现改善相关的功能变化。我们研究了48例接受STN DBS治疗的患者，这些患者夜间停药，并接受PET扫描以测量双侧STN DBS刺激下的rCBF反应。PET扫描在双侧DBS关闭和开启状态下以平衡顺序进行，随后使用统一帕金森病评定量表3（UPDRS 3）对运动表现进行临床评分。我们研究了UPDRS 3评分在强直、运动迟缓、姿势稳定性和步态方面的改善是否与预先确定区域的rCBF反应相关。这些区域是根据先前一项研究选定的，该研究显示STN DBS可引起丘脑、中脑和辅助运动区（SMA）的rCBF显著变化。由于越来越多的证据表明脚桥核区域（PPN）参与运动，我们也选择了该区域。在本研究中，双侧STN DBS改善了强直（62%）、运动迟缓（44%）、步态（49%）和姿势稳定性（56%）（配对t检验：P<0.001）。正如预期的那样，双侧STN DBS还增加了双侧丘脑、右侧中脑的rCBF，并降低了右侧运动前皮质的rCBF（P<0.05，校正后）。强直改善与SMA区rCBF降低之间存在显著相关性（r(s)=-0.4，P<0.02），运动迟缓改善与丘脑rCBF增加之间存在显著相关性（r(s)=0.31，P<0.05）。此外，姿势反射改善与PPN区rCBF降低相关（r(s)=-0.38，P<0.03）。选择性运动表现与特定区域rCBF之间的这些适度相关性表明，帕金森病不同运动体征的改善可能存在区域选择性。
