Clinical and cerebral activity changes induced by subthalamic nucleus stimulation in advanced Parkinson's disease: a prospective case-control study.
BACKGROUND
High-frequency stimulation of the subthalamic nucleus (STN-DBS) improves motor symptoms in advanced Parkinson's disease (PD), but the mechanisms are still unclear. Functional imaging evidenced pathological overactivity in motor cortical areas in advanced PD that can be normalized by effective therapies.


METHODS
We studied resting state cerebral blood flow pre-operatively and 12 months after surgery in 40 patients with advanced PD using ECD-SPECT. SPECT scans were also acquired 1 year apart in 21 matched PD controls who did not undergo surgery. Statistical analysis was performed using statistical parametric mapping (SPM2) software. In addition, we correlated brain perfusion changes after surgery with clinical improvement, assessed using the unified PD rating scale motor score (UPDRS-III).


RESULTS
Patients showed marked motor improvement and medication reduction after surgery. Stimulated PD patients revealed bilateral rCBF decrements in motor cortical areas and prefrontal cortex bilaterally compared to pre-surgical condition as well as versus PD controls (p<.01 FDR corrected). Perfusion increases were found in cerebellum, temporal and occipital lobes. Clinical improvement was associated with perfusion decrements in primary motor and premotor cortices.


CONCLUSIONS
Effective STN-DBS is associated with neuronal activity changes in brain regions implicated in movement programming and performance. We hypothesize that clinical benefit might be associated with stimulation-induced normalization of the abnormal overactivity within the cortico-basal ganglia-thalamo-cortical motor loop in advanced PD.
Cilia
Roberto
R
Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy. roberto.cilia@tiscali.it
Marotta
Giorgio
G
Landi
Andrea
A
Isaias
Ioannis U
IU
Mariani
Claudio B
CB
Vergani
Francesco
F
Benti
Riccardo
R
Sganzerla
Erik
E
Pezzoli
Gianni
G
Antonini
Angelo
A
D000368:Aged; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016022:Case-Control Studies; D002531:Cerebellum / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D046690:Deep Brain Stimulation / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology; D009048:Motor Skills / Q000502:physiology; D010296:Parietal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology; D010300:Parkinson Disease / Q000503:physiopathology / Q000628:therapy*; D017397:Prefrontal Cortex / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology; D011446:Prospective Studies; D020127:Recovery of Function / Q000502:physiology; D020531:Subthalamic Nucleus; D013702:Temporal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D016896:Treatment Outcome