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1.  Quantitative analysis of gait and balance response to deep brain stimulation in Parkinson's disease 
Gait & posture  2012;38(1):109-114.
Gait and balance disturbances in Parkinson’s disease (PD) can be debilitating and may lead to increased fall risk. Deep brain stimulation (DBS) is a treatment option once therapeutic benefits from medication are limited due to motor fluctuations and dyskinesia. Optimizing DBS parameters for gait and balance can be significantly more challenging than for other PD motor symptoms. Furthermore, inter-rater reliability of the standard clinical PD assessment scale, Unified Parkinson’s Disease Rating Scale (UPDRS), may introduce bias and washout important features of gait and balance that may respond differently to PD therapies. Study objectives were to evaluate clinician UPDRS gait and balance scoring inter-rater reliability, UPDRS sensitivity to different aspects of gait and balance, and how kinematic features extracted from motion sensor data respond to stimulation. Forty-two subjects diagnosed with PD were recruited with varying degrees of gait and balance impairment. All subjects had been prescribed dopaminergic medication, and twenty subjects had previously undergone DBS surgery. Subjects performed seven items of the gait and balance subset of the UPDRS while wearing motion sensors on the sternum and each heel and thigh. Inter-rater reliability varied by UPDRS item. Correlation coefficients between at least one kinematic feature for six of the seven items and UPDRS were greater than 0.75. Kinematic features improved (p < 0.05) from DBS-OFF to DBS-ON for three UPDRS items. Despite achieving high correlations with the UPDRS, evaluating individual kinematic features may help address inter-rater reliability issues and rater bias associated with focusing on different aspects of a motor task.
doi:10.1016/j.gaitpost.2012.10.025
PMCID: PMC3596454  PMID: 23218768
2.  Influence of orbital eye position on vertical saccades in progressive supranuclear palsy 
Disturbance of vertical saccadesis a cardinal feature of progressive supranuclear palsy (PSP). We investigated whether the amplitude and peak velocity of saccades is affected by the orbital position fromwhich movements start in PSP patients and age-matched control subjects. Subjects made vertical saccades in response to ± 5 degree vertical target jumps with their heads in one of three positions: head “center,” head pitched forward ~15 degrees, and head pitched back ~ 15 degrees.All patients showed some effect of starting eye position, whether beginning in the upward or downward field of gaze, on saccade amplitude, peak velocity (PV), and net range of movement. Generally, reduction of amplitude and PV were commensurate and bidirectional in the affected hemifield of gaze. Such findings are unlikelyto be due to orbital factors and could be explained by varying degrees of involvement of rostral midbrain nucleiin the pathological process.
doi:10.1111/j.1749-6632.2011.06120.x
PMCID: PMC3187876  PMID: 21950977
saccades; midbrain; neural integrator; eyeball; parkinsonian disorders
3.  Effect of Low Concentrations of Apomorphine on Parkinsonism in a Randomized, Placebo-Controlled, Crossover Study 
Archives of Neurology  2008;65(2):193-198.
Objective
To determine whether low concentrations of a dopamine agonist worsen parkinsonism, which would suggest that activation of presynaptic dopamine autoreceptors causes a super-off state.
Design
Randomized, double-blind, placebo-controlled, crossover clinical trial.
Setting
Academic movement disorders center.
Patients
Patients with Parkinson disease and motor fluctuations.
Intervention
Fourteen patients with Parkinson disease and motor fluctuations were randomized to receive 1 of 6 possible sequences of placebo, low-dose (sub-threshold) apomorphine hydrochloride, and high-dose (threshold to suprathreshold) apomorphine hydrochloride infusions. Subthreshold doses of apomorphine hydrochloride (12.5 μg/kg/h every 2 hours and 25 μg/kg/h every 2 hours), threshold to suprathreshold doses of apomorphine hydrochloride (50 μg/kg/h every 2 hours and 100 μg/kg/h every 2 hours), and placebo were infused for 4 hours daily for 3 consecutive days.
Main Outcome Measures
Finger and foot tapping rates.
Results
There was no decline in finger or foot tapping rates during the low-dose apomorphine hydrochloride infusions relative to placebo. The high-dose infusions increased foot tapping (P<.001) and trended toward increasing finger tapping compared with placebo infusions.
Conclusions
Subthreshold concentrations of apomorphine did not worsen parkinsonism, suggesting that pre-synaptic dopamine autoreceptors are not important to the motor response in moderate to advanced Parkinson disease.
doi:10.1001/archneurol.2007.58
PMCID: PMC3390309  PMID: 18268187
4.  Effects of a NR2B Selective NMDA Glutamate Antagonist, CP-101,606, on Dyskinesia and Parkinsonism 
Movement Disorders  2008;23(13):1860-1866.
Glutamate antagonists decrease dyskinesia and augment the antiparkinsonian effects of levodopa in animal models of Parkinson’s disease (PD). In a randomized, double-blind, placebo-controlled clinical trial we investigated the acute effects of placebo and two doses of a NR2B subunit selective NMDA glutamate antagonist, CP-101,606, on the response to two-hour levodopa infusions in 12 PD subjects with motor fluctuations and dyskinesia. Both doses of CP-101,606 reduced the maximum severity of levodopa-induced dyskinesia approximately 30% but neither dose improved parkinsonism. CP-101,606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects.
doi:10.1002/mds.22169
PMCID: PMC3390310  PMID: 18759356
Parkinson’s disease; levodopa; dyskinesia; NR2B subunit selective glutamate antagonist; CP-101,606; amnesia; dissociation

Results 1-4 (4)