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1.  Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD (e–Pub ahead of print)  
Neurology  2010;75(19):1711-1716.
Objective:
Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls).
Methods:
Following overnight withdrawal of antiparkinsonian medication, patients were studied with H2 15O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback.
Results:
We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity.
Conclusions:
We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions—outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)—together with restricted access of those areas to executive control (external pallidum)—may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.
GLOSSARY
= analysis of variance;
= dopamine agonist;
= Gambling Symptom Assessment Scale;
= external pallidum;
= Montréal Neurological Institute;
= orbitofrontal cortex;
= Parkinson disease;
= regional cerebral blood flow;
= rostral cingulated zone;
= Unified Parkinson's Disease Rating Scale.
doi:10.1212/WNL.0b013e3181fc27fa
PMCID: PMC3033606  PMID: 20926784
2.  Clinical and neuropsychological follow up at 12 months in patients with complicated Parkinson's disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus 
Background
The clinical condition of advanced Parkinson's disease (PD) patients is often complicated by motor fluctuations and dyskinesias which are difficult to control with available oral medications.
Objective
To compare clinical and neuropsychological 12 month outcome following subcutaneous apomorphine infusion (APO) and chronic deep brain stimulation of the subthalamic nucleus (STN‐DBS) in advanced PD patients.
Methods
Patients with advanced PD and medically untreatable fluctuations underwent either APO (13 patients) or STN‐DBS (12 patients). All patients were clinically (UPDRS‐III, AIMS, 12 h on‐off daily) and neuropsychologically (MMSE, Hamilton‐17 depression, NPI) evaluated at baseline and at 12 months. APO was discontinued at night.
Results
At 12 months APO treatment (74.78±24.42 mg/day) resulted in significant reduction in off time (−51%) and no change in AIMS. Levodopa equivalent medication doses were reduced from 665.98±215 mg/day at baseline to 470±229 mg/day. MMSE, NPI, and Hamilton depression scores were unchanged. At 12 months STN‐DBS resulted in significant clinical improvement in terms of reduction in daily off time (−76%) and AIMS (−81%) as well as levodopa equivalent medication doses (980±835 to 374±284 mg/day). Four out of 12 patients had stopped oral medications. MMSE was unchanged (from 28.6±0.3 to 28.4±0.6). Hamilton depression was also unchanged, but NPI showed significant worsening (from 6.58±9.8 to 18.16±10.2; p<0.02). Category fluency also declined.
Conclusions
Both APO and STN‐DBS resulted in significant clinical improvement in complicated PD. STN‐DBS resulted in greater reduction in dopaminergic medications and provided 24 h motor benefit. However, STN‐DBS, unlike APO, appears to be associated with significant worsening on NPI resulting from long term behavioral problems in some patients.
doi:10.1136/jnnp.2005.078659
PMCID: PMC2077512  PMID: 16543520
apomorphine; deep brain stimulation of the subthalamic nucleus; neuropsychology; Parkinson's disease; STN‐DBS

Results 1-2 (2)