TY - JOUR
T1 - Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease
AU - Karimi, M.
AU - Golchin, N.
AU - Tabbal, S. D.
AU - Hershey, T.
AU - Videen, T. O.
AU - Wu, J.
AU - Usche, J. W.M.
AU - Revilla, F. J.
AU - Hartlein, J. M.
AU - Wernle, A. R.
AU - Mink, J. W.
AU - Perlmutter, J. S.
N1 - Funding Information:
This study was supported by NIH/NINDS grants NS050425, NS41509, P30NS057105 (the Neuroscience Blueprint Core Grant to Washington University), CO6 RR020092 and UL1 RR024992 (CTSA at Washington University); the Greater St. Louis Chapter of American Parkinson’s Disease Association (APDA); the APDA Advanced Center for Parkinson’s disease Research at Washington University; and the Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund and the Jack Buck Fund for Parkinson’s Research). Dr Karimi and Dr Revilla have received partial fellowship funding from Medtronic, Inc., the manufacturer of the implanted stimulators; no other authors have any conflicts of interest to disclose.
PY - 2008/10
Y1 - 2008/10
N2 - 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.
AB - 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.
KW - Deep brain stimulation
KW - Parkinson's disease
KW - Pedunculopontine nucleus
KW - Positron emission tomography
KW - Subthalamic nucleus
UR - http://www.scopus.com/inward/record.url?scp=54949153171&partnerID=8YFLogxK
U2 - 10.1093/brain/awn179
DO - 10.1093/brain/awn179
M3 - Article
C2 - 18697909
AN - SCOPUS:54949153171
SN - 0006-8950
VL - 131
SP - 2710
EP - 2719
JO - Brain
JF - Brain
IS - 10
ER -