Brain Advance Access published online on August 12, 2008
Brain, doi:10.1093/brain/awn179
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Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease
1Department of Neurology, 2Department of Psychiatry, 3Department of Radiology, 4Department of Anatomy and Neurobiology, 5Program in Physical Therapy, Washington University School of Medicine, St Louis, MO, USA, 6Department of Neurology, University of Cincinnati College of Medicine and Cincinnati VA Medical Center, Cincinnati, OH, USA, 7Department of Neurology, Department of Neurobiology & Anatomy, Department of Brain & Cognitive Sciences and Department of Pediatrics, University of Rochester, Rochester, NY, USA
Correspondence to:
Joel S. Perlmutter MD, Campus Box 8225, Washington University School of Medicine, 4525 Scott Avenue, St Louis, MO 63110, USA E-mail: joel{at}npg.wustl.edu
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 (rs = –0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (rs = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (rs = –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.
Key Words: Parkinson's disease; deep brain stimulation; subthalamic nucleus; pedunculopontine nucleus; positron emission tomography
Abbreviations: DBS, deep brain stimulation; Gpi, globus pallidus pars interna; H&Y, Hoehn and Yahr; PPN, pedunculopontine nucleus; rCBF, regional cerebral blood flow; SMA, supplementary motor area; SMC, sensorimotor cortex; SNr, substantia nigra pars reticulata; STN, subthalamic nucleus; UPDRS, Unified Parkinson Disease Rating Scale; VOI, volume of interest
Received February 22, 2008. Revised July 8, 2008. Accepted July 12, 2008.